Charting molecular free-energy landscapes with an atlas of collective variables.
Collective variables (CVs) are a fundamental tool to understand molecular flexibility, to compute free energy landscapes, and to enhance sampling in molecular dynamics simulations. However, identifying suitable CVs is challenging, and is increasingly addressed with systematic data-driven manifold learning techniques. Here, we provide a flexible framework to model molecular systems in terms of a collection of locally valid and partially overlapping CVs: an atlas of CVs. The specific motivation for such a framework is to enhance the applicability and robustness of CVs based on manifold learning methods, which fail in the presence of periodicities in the underlying conformational manifold. More generally, using an atlas of CVs rather than a single chart may help us better describe different regions of conformational space. We develop the statistical mechanics foundation for our multi-chart description and propose an algorithmic implementation. The resulting atlas of data-based CVs are then used to enhance sampling and compute free energy surfaces in two model systems, alanine dipeptide and β-D-glucopyranose, whose conformational manifolds have toroidal and spherical topologies.
LaCàN, Universitat Politècnica de Catalunya-BarcelonaTech, Barcelona, Spain.
Behrooz
B
Hashemian
LaCàN, Universitat Politècnica de Catalunya-BarcelonaTech, Barcelona, Spain.
Daniel
D
Millán
LaCàN, Universitat Politècnica de Catalunya-BarcelonaTech, Barcelona, Spain.
Marino
M
Arroyo
D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D002236:Carbohydrate Conformation; D005947:Glucose / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D013816:Thermodynamics
C024314:N-acetylalanyl-N-methylamide; D005947:Glucose; D000409:Alanine