SMBp Group Meeting: Justin Lindsay & Erik Thiede

Thursday Aug 11, 2022, 12:00 PM → 1:00 PM America/New_York

3rd Floor Classroom/3-Flatiron Institute (162 5th Avenue)

Speaker: Justin Lindsay & Erik Thiede 

Topic: Towards a better IDP builder: Sequential Monte Carlo + MD

Abstract: Intrinsically disordered proteins are a class of biopolymers which are notoriously difficult to structurally characterize due to the vast and varied nature of their conformational landscapes. Polymer chain-growth methods are a common tool used to quickly generate large ensembles of the IDP of interest. Such methods are limited, however, as the generated ensembles do not typically follow the expected Boltzmann distributions. While re-weighting can sometimes produce more accurate samples, the tendency of chain-growth methods to produce over-extended conformations can lead to ensembles dominated by one or few conformers for the majority of IDPs. Results can be improved with the inclusion of experimental observations as constraints, but such experimental data is not available for the vast majority of IDPs. To address this problem, we propose a chain-growth method that utilizes sequential Monte Carlo and molecular dynamics to produce IDP ensembles that more closely mirror their expected Boltzmann distributions. Through the incorporation of MD between growth steps to relax structures as they are built, we will be able to produce more physically probable configurations which can greatly improve the effectiveness of resampling for recovering expected ensembles of IDPs of any type.