Comparison of Different Reweighting Approaches for the Calculation of Conformational Variability of Macromolecules from Molecular Simulations |
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Authors: | Dr Denise Medeiros Selegato Dr Cesare Bracco Prof Carlotta Giannelli Prof Giacomo Parigi Prof Claudio Luchinat Dr Luca Sgheri Dr Enrico Ravera |
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Institution: | 1. Magnetic Resonance Center (CERM) and Interuniversity Consortium for Magnetic Resonance of Metallo Proteins (CIRMMP), Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy;2. Dipartimento di Matematica e Informatica “U. Dini”, Università degli Studi di Firenze, Viale Morgagni 67/a, 50134 Florence, Italy;3. Istituto per le Applicazioni del Calcolo (CNR) sede di Firenze, via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy |
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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. |
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Keywords: | ensemble optimization macromolecules maximum entropy maximum parsimony molecular simulations |
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