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Send us Fan MailIn Episode 30, Zan Luthey-Schulten tells us the story of her most ambitious project over the last fifteen years or so: creating whole-cell simulations. In a reminder that true science knows no boundaries, she ties together a whole range of scientific disciplines - hardware optimization, stochastic calculus, reaction rates, advanced Hamiltonians, synthetic biology, cell imaging data, to eventually approach bioengineering and medicine. Zan also shares her stories and thoughts about how to pick collaborators, how to work together, and what we computational scientists can learn both from each other and from the broader field of biology or biophysics.

Send us Fan MailJerome starts our conversation by reviewing the history of the ABF method and its advantages compared to the main competitors, and connects it to the development of COLVARS, historically very parallel to how the development of the Plumed tool stemmed from the needs of the metadynamics community. We discuss the benefits of graphical interfaces in biomolecular workflows, and touch upon the question of connecting multiple software environments and communities. We then move on to discuss membrane systems and the challenges they pose, both historically and today, and end up on the alchemical side, talking about the latest approaches to alchemical free energy calculations from several exciting angles. Eventually, we agree that regardless of software developments, it's learning and helping others learn to understand molecular systems that's the most rewarding part of the job of a biophysicist.

Send us Fan MailIn Episode 28, Yuji Sugita shares the story of how he developed temperature replica exchange in the lab of Yuko Okamoto, connecting to his early experience from working with Nobuhiro Go, the father of Go models. We then talk about the process of building up workflows for simulating massive atomistic systems, a multi-year collaboration with Michael Feig, and ponder the question of when one should go about writing their own scientific software rather than reusing existing software packages. Talking about molecular crowding naturally brings us to current and future directions, which for Yuji include simulating increasingly multi-component condensates and exploring multi-resolution schemes in GENESIS. Towards the end, he highlights the need for young researchers to engage with the international community through long-distance collaborations, regardless of where one ends up living and working.

Send us Fan MailIn episode 27, Kresten starts by explaining his path from a wet lab biochemist to a computational biophysicist, a story full of open-ended explorations and helpful mentors. He gives us some background on how both the legacy and latest models developed, highlighting how in each case the driving force were experimental results that either weren't quite matching simulations, or were plenty enough to allow for top-down training. We walk through some of the functions and applications of intrinsically disordered regions, or IDRs in short, and their relevance for medical research. Then towards the end, Kresten shares some tips and observations from his work in grant evaluation, insisting that internal peer review remains the best source of feedback, but in the end it's one's scientific intuition that has to guide us.

Send us Fan MailIn episode 26, we talk about the origins of Pratyush's passion for statistical mechanics, deeply rooted in his background in material science, and think about how we can promote a profound understanding of statmech theory among people working in computational biophysics. From there, we explore ways of re-introducing physical rigor into modern data-driven approaches, which is the main concern that Pratyush says drives his research agenda. He ends up sharing a ton of interesting points on working with the industry, the value of education and knowledge sharing, or the philosophy of complex and cognitive systems, and ends up with a call for more time for silent thinking, where - he says - most of his original ideas came from.

Send us Fan MailIn episode 25, Ivet and me start with a general overview of the elastic network theory and its applications to biology, as well as its strengths and limitations. Ivet then tells us about the specific takeaways from the different lines of her research, talking about evolutionary dynamics signatures, mode excitations in allosteric effects, as well as her recent research on the relevance of hinge regions for drug discovery. We talk about the relevance of the proteins-as-graphs picture for machine learning, and end up with a few general reflections about the complementary roles of persistence and alertness in scientific careers.

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Send us Fan MailIn episode 24, Katarzyna talks about the everyday concerns and common threads of an editor's job, from continuously learning about the rapid developments in the field to navigating the review process. She shares some inside stories about the experimental features that journals tinker with these days, and it's good to know that many interesting ideas are being tested out there in the wild. We then discuss a bit about the evolution of the publishing process, including its perception among us research scientists. We largely leave the questions of profits and finance out of the conversation, so this is purely a conversation between two science aficionados who care deeply about the scientific enterprise being transparent, just, open to novelty and focused on quality evidence.

Send us Fan MailIn episode 23, Zoe and me discuss the current status and promises of drug design, a field where many things seem trivial but nothing is really simple. Zoe talks about the challenges that precision medicine is facing, and how it fits into the grand landscape of future therapies. We go through some success stories, and I ask Zoe how the recent additions to drug design workflows help them in everyday scientific practice, both in terms of physics-based and data-driven models. We then spend a moment talking about the opportunities and responsibilities of a journal editor, and what are the lessons Zoe learned from creating her startup.

Send us Fan MailIn episode 22, we start by talking about the 2022 review of enhanced sampling methods that Lucie co-authored, one that provides long-needed organizing principles and unifying vocabulary for applications in this field. We also outline some challenges and community needs still waiting for the bold souls out there looking for ambitious projects. Lucie then moves on to share her experience with alternative publishing models, both as a member of Biophysics Colab and a former editor of eLife, and we dwell a bit on the challenges and possible solutions to what some would call a crisis in publishing, where evaluation metrics and publishing companies created unsustainable or even counterproductive incentive structures in sharing scientific results. We end on personal notes: already last year when I was visiting her lab in Stockholm, Lucie agreed to be on the very first list of interviewees, but it took me so long to figure it out that eventually Lucie gave birth to her twins and went on a maternal leave, so now that she's back more than a year later, I also asked her to share a few reflections on becoming a parent in academia.

Send us Fan MailIn episode 21, Tamar first explains how her unique background impacted the way she approached and conceptualized problems in biology, and how her research projects were born in the first place. We talk about the more recent research coming from Tamar's group on frameshifting, a fascinating process by which the readout of the genetic code can be offset by one or two letters to produce multiple proteins from a single viral gene. We then move on to discuss whether it's algorithms or compute that have contributed more to the growth of computational biophysics. Tamar's textbook and the multiple perspective articles she's written over the years serve us to dwell on the importance of writing for clarity and interdisciplinary collaboration. We end on a people-centric note, talking about the social bonds involved in both running and experimental collaborations.

Send us Fan MailIn episode 20, I start by asking Rommie how their research on the SARS-CoV-2 virus first unfolded during the early days of the pandemic, and from this story, we move on to discuss her original motivation to study large complex systems. We touch upon the exciting experimental developments that enable the realistic modeling of systems as big as entire viruses, and highlight some unexpected findings that came out of the large-scale simulations. Rommie also shares her reflections about the collaboration-driven nature of her lab and the complexities involved in interdisciplinary communication, and we wrap up with a few thoughts about the AI-driven brain drain from academia to industry.

Send us Fan MailIn episode 19, Alex and I discuss the history and future of developments in the CHARMM family of force fields, and whether Alex believes there is more physics that we need to include in our classical energy functions to work around our current challenges in biomolecular modeling. Throughout the conversation, he's advocated for a pragmatic, down-to-earth approach, with the idea of "big molecules, small physics". Alex also highlights the need to augment AI tools with HI, or human intelligence, arguing that so far most attempts at automating model development too much end up with parameters that are unphysical and non-transferable. Yet another interesting point is our often surprising reliance on truly ancient experimental data, and we try to make a point that these very non-sexy physical chemistry measurements straight from the 60s and 70s could truly advance the field if anyone was willing to fund them and actually get them done.

Send us Fan MailIn Episode 18, Erik Lindahl reminds us that despite our dependence on computational power and advanced technology, real breakthroughs are often waiting for those who have the patience to think carefully, come up with eye-opening ideas, and follow their sense of purpose. We discuss the different ways to be smart in science, highlighting the paradoxical need for both complexity and simplicity in thinking, and talk about what kind of questions in biology will keep us all busy for decades to come. Finally, Erik shares the story behind his series of lectures on concepts in molecular biophysics, a great component of the curriculum of every scientist in the field.

Send us Fan MailIn episode seventeen, Caroline Lynn Kamerlin talks about the art of asking bold and impactful scientific questions, as well as how to engage in truly interdisciplinary research, something she sees as a consequence of her formal background in natural philosophy. We talk about the emerging concepts around enzyme promiscuity, how this view has steadily become accepted in the field, and how it affects not only research but also human lives. That leads us to consider the ever-emerging problem of bacterial resistance and public health, and since public health is just two steps away from science education, we do venture there too.

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Send us Fan MailIn the sixteenth episode, Janusz Bujnicki tells me about his early switch to bioinformatics, a stroke of serendipity that defined his future career, and how he later managed to reincorporate both biophysics and experimental biology into his research agenda. We talk about the current state of the field of RNA structural prediction, and how we need to bring together physics and data to tackle the ever more complex biological questions that show up on the horizon. Then, we switch gears to discuss the fascinating world of science advisors for policy-making, or to what extent our scientific knowledge can be employed to shape long-term policies, including the blurry borders between science, philosophy and politics. I think it's a laudable aspiration for many of us to understand how we can have a tangible impact on the real world while keeping our humility in check.

Send us Fan MailIn the fifteenth episode, Paulo Souza and I discuss the challenges inherent in managing a project of such a scope, and the philosophy behind the systematic way in which Martini is continuously improved and reparameterized. Paulo describes how a user-centric approach helps refine and troubleshoot the model through its widescale adoption, and how different inherent limitations of coarse-grained modeling can be addressed to progressively make the force field more predictive and less reliant on user-defined biases. Then, we talk about the interplay between force field development and modern trends in biology, biomedicine and computational sciences - from small molecules to lipid nanoparticles, huge systems such as organelles or viruses, and molecular complexity, understood as going beyond simplified model systems and approaching biologically relevant mixtures and compositions.

Send us Fan MailIn the fourteenth episode, Syma Khalid and I talk about the challenges we're faced with when trying to understand the environment of the bacterial cell envelope, and the outer membrane in particular. We discuss how the lessons taken from the computational study of these structures can inform the design of future antibacterial agents. Then, we move on to consider strategies for making the scientific environment of one's research group a place to thrive, develop, and live a happy and fulfilling life.

Send us Fan MailIn the thirteenth episode, Daniel Zuckerman and I talk about textbooks on statistical biophysics and a physics-based vision of biology, a few of which he himself authored. Daniel reveals that his passion for clarity in writing comes from his early humanities background, and makes a case for how well-thought and physically motivated narratives can unlock profound insights into the inner workings of biology. Then, we move on to discuss the physical theory behind trajectory ensembles, Daniel's preferred lens through which to view statistical mechanics. We dissect the strengths and limitations of this approach, and let ourselves speculate about its future evolution.

Send us Fan MailIn the twelfth episode, Vlad Cojocaru and I discuss how the simulation field can integrate further layers of complexity in modeling transcription control and genome organization in humans. Vlad shares his insights on the computational biology of transcription factors, including DNA-mediated allostery and pioneer transcription factors, which are crucial for cellular reprogramming. Our discussion then shifts to the underexplored topic of researchers' returning to our home countries as group leaders. We examine the hopes, fears, and conditions for success in making this transition, aiming to rewrite common narratives from our unique perspectives.

Send us Fan MailIn the eleventh episode, Justin Lemkul and I talk about the motivations and challenges behind providing technical help on online forums and mailing lists. Justin shares his story of becoming a prolific technical advisor for the Gromacs community, which evolves into a discussion about automatability, the role of expertise in running and documenting simulation-based projects, and the incentives for people who contribute their time to helping the community. We then move on to discuss polarizable force fields for nucleic acids, including the problems they might help solve and the practical ways in which we might arrive at these solutions. We conclude by pointing out the need for more nuanced undergraduate curricula that reflect the current open questions in nucleic acids research to attract students who will make the future discoveries.

Send us Fan MailIn the tenth episode, Ariane Nunes-Alves and I talk about a kinetics-centric view of drug design, making the case that modeling kinetics in atomistic simulation is an important frontier that, despite clear biomedical relevance, is rarely explicitly addressed either in model parameterization or with the latest AI methods. We discuss the need to turn to a more explicit image of the drug's pathway towards its target, including not only affinities and residence times, but also the cellular environment. Then, we switch to the social sphere to discuss how much of a PI's professional time circles around interpersonal interactions, and where can we computational scientists go to find our community in the era of fragmentation and specialization of social media.

Send us Fan MailIn the ninth episode, Michele Vendruscolo and I discuss the current state of research on misfolding diseases, typically associated with excessive protein aggregation and formation of insoluble amyloids. Michele presents an optimistic perspective in which the convergence of recent clinical and software developments opens up new avenues for efficient treatment of such debilitating conditions as Alzheimer's and Parkinson's disease. This interconnection between the everyday work of scientists and the experience and outlook of affected individuals inspires us to reflect on the societal responsibilities of a scientist, from disseminating our results to inspiring newcomers to engage with urgent global crises to mentoring the next generation of problem-solvers and revolutionary thinkers.

Send us Fan MailIn this episode, I'm attempting to string together the most common threads brought up by my guests in the first eight interviews on the podcast. Reflecting on these conversations, I'm suggesting some grand challenges for the field in the years to come.

Send us Fan MailIn the eight episode, Rossen Apostolov and I depart from the standard format to talk about the core concepts behind BioExcel, the European Center of Excellence for computational biology. We discuss their main objectives and challenges, from working with code to organizing schools and webinars, talk about the challenges of sustaining funding through maintaining excellence in research, and review ways to share the gained experience with the broader computational world to inspire similar ventures elsewhere. It is a partial attempt to answer questions raised in previous conversations by pointing to existing models for international collaboration across many subfields.

Send us Fan MailIn the seventh episode, Aleksei Aksimentiev and I delve into the intersection of physics, biology, and nanotechnology, exploring the innovative world of nanopores and biomolecular sequencing. Aleksei shares his journey from particle physics in Ukraine to leading-edge research in the US, and underscores how on the unpredictable path of scientific discovery, openness to new ideas can lead to groundbreaking advancements. Alongside, we discuss the pivotal role of mentorship in fostering scientific curiosity and the pursuit of ambitious goals, illustrating how a supportive mentor can be the key to unlocking potential and driving forward the frontier of biophysics.

Send us Fan MailIn the sixth episode, Giulia Palermo and I discuss the challenges of studying truly multiscale biomolecular systems, such as the CRISPR/Cas9 complex she famously got involved with. While such problems can take us way out of our comfort zones, they also provide us with clear pathways to innovative and transformative science, something very much needed in the new revolutionary era of RNA biology. In this vein, Giulia also reflects on the nature of scientific creativity, the component that goes beyond our formal training but that can eventually spell the difference between a groundbreaking discovery and run-of-the-mill research.

Send us Fan MailIn the fifth episode, Paul Robustelli and I discuss how the once very sharp boundary between academia and industry has been becoming increasingly porous, and what implications it will have for future careers in science. Paul shares his experiences and observations about the competing models of funding scientific research, and makes a point that they can eventually synergize rather than compete. We also talk about the often neglected creative or artistic nature of scientists, and how we can use it to better connect with other scientists in a more genuine way.

Send us Fan MailIn the fourth episode, Modesto Orozco and I talk about the rough path to the predictive power modern computational science has achieved in biology, and the immense possibilities it opens to today's computational biologists working across the scales of space and time. Modesto also reflects on why sharing simulation data is crucial to make sure that our results are trustworthy, and how access to other people's simulations can become a gold mine in the data-driven era of computer modeling.

Send us Fan MailIn the third episode, Wojtek Kopeć and I discuss the overlooked yet exciting social aspect of scientific collaboration, and what the world of academia could learn from the industry and statisticians to avoid falling behind. Wojtek also shares his personal experience of starting a lab as a new PI, and we reflect on the role of honesty on social media in addressing the hardships of being a scientist.

Send us Fan MailIn the second episode, Max Bonomi and I discuss efforts to achieve interoperability and portability in the computational community, and how the AI structural revolution will unfold to bring us realistic molecular ensembles. We then move on to ask how the entire range of contributions to science can be recognized, particularly at the early career stage.

Send us Fan MailIn the first episode, Pilar Cossio and I discuss the radical progress in integrating simulations with experiments, and the excitement about recent progress in modeling cryo-EM tomography data. We share thoughts on the sustainability of our publishing practices, and comment on the challenges of funding the maintenance of scientific code libraries.

Send us Fan MailWhat is this all about? Does the computational community need a podcast? Along with the first interview, I'm sharing the idea behind PSI, and explaining why the time is ripe for a new marketplace of ideas to drive the changes in how we do science. Everyone is invited, from ambitious undergraduates to seasoned veterans!