Comparison of Different Reweighting Approaches for the Calculation of Conformational Variability of Macromolecules from Molecular Simulations. Issue 1 (27th November 2020)

• Record Type: Journal Article
• Authors: Medeiros Selegato, Denise; Bracco, Cesare; Giannelli, Carlotta; Parigi, Giacomo; Luchinat, Claudio; Sgheri, Luca; Ravera, Enrico
• Is Part Of: Chemphyschem. Volume 22:Issue 1(2021)
• Page Start: 127
• Page End: 138
• Publication Date: 2020-11-27
• Subjects: ensemble optimization -- macromolecules -- maximum entropy -- maximum parsimony -- molecular simulations; Chemistry, Physical and theoretical -- Periodicals; 541.05
• DOI: 10.1002/cphc.202000714
• Languages: English
• ISSNs: 1439-4235

Abstract

Abstract: Conformational variability and heterogeneity are crucial determinants of the function of biological macromolecules. The possibility of accessing this information experimentally suffers from severe under‐determination of the problem, since there are a few experimental observables to be accounted for by a (potentially) infinite number of available conformational states. Several computational methods have been proposed over the years in order to circumvent this theoretically insurmountable obstacle. A large share of these strategies is based on reweighting an initial conformational ensemble which arises from, for example, molecular simulations of different qualities and levels of theory. In this work, we compare the outcome of three reweighting approaches based on radically different views of the conformational heterogeneity problem, namely Maximum Entropy, Maximum Parsimony and Maximum Occurrence, and we do so using the same experimental data. In this comparison we find both expected as well as unexpected similarities. Abstract : The reweighting molecular simulations can be based on different views of ensemble averaging. Comparing different methods on the same datasets yields expected differences and unexpected similarities.