Borna Novak

Program: Computational and Systems Biology

Current advisor: Alex Holehouse, PhD

Undergraduate university: University of Sciences-Philadelphia, 2019

Enrollment year: 2019

Research summary
Exploring the Sequence-Ensemble Relationship of Intrinsically Disordered Proteins

Intrinsically disordered proteins (IDPs) and regions (IDRs) are found across all domains of life. They comprise over 30% of the human proteome and are implicated in many important cellular functions. In contrast to folded proteins, IDRs lack a stable 3D structure and are instead described in terms of a conformational ensemble, a heterogenous collection of energetically accessible interconverting conformations. This unique structural plasticity facilitates diverse molecular recognition and function, thus, a convenient way to understand IDRs function is through their ensembles. However, the characterization of IDR ensembles often requires low-throughput experiments or technically challenging simulations. Recent advances in multiscale generative modeling have enabled raping generation of multiple modalities, such as images, videos and text. Leveraging such approaches permits rapid construction of IDR ensembles, enabling structural bioinformatic analyses of disordered proteins. This, in turn, opens the door to the computational interrogation of IDR function through the lens of emergent biophysical properties in addition to traditional bioinformatic approaches. Moreover, such modelling approach enables ensemble-based design applications in synthetic biology.

Graduate publications
Smith LG, Novak B, Osato M, Mobley DL, Bowman GR. 2024 PopShift: A Thermodynamically Sound Approach to Estimate Binding Free Energies by Accounting for Ligand-Induced Population Shifts from a Ligand-Free Markov State Model. J Chem Theory Comput, 20(3):1036-50. PMCID: PMC10867841

Meller A, Lotthammer JM, Smith LG, Novak B, Lee LA, Kuhn CC, Greenberg L, Leinwand LA, Greenberg MJ, Bowman GR. 2023 Drug specificity and affinity are encoded in the probability of cryptic pocket opening in myosin motor domains. Elife, 12():e83602. PMCID: PMC9995120

Chung MKJ, Miller RJ, Novak B, Wang Z, Ponder JW. 2023 Accurate Host-Guest Binding Free Energies Using the AMOEBA Polarizable Force Field. J Chem Inf Model, 63(9):2769-2782. PMCID:

Vithani N, Ward MD, Zimmerman MI, Novak B, Borowsky JH, Singh S, Bowman GR. 2021 SARS-CoV2 Nsp16 activation mechanism and a cryptic pocket with pan-coronavirus antiviral potential. Biophys J, ():S0006-3495(21)00254-X. PMCID: PMC8007187