Fitting Corrections to an RNA Force Field Using Experimental Data
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Published on: February 16, 2024
Andrea Cesari1, Sandro Bottaro2, Kresten Lindorff-Larsen2
1Scuola Internazionale Superiore di Studi Avanzati (SISSA), via Bonomea 265 , 34136 Trieste , Italy.
Abstract:
Empirical force fields for biomolecular systems are usually derived from quantum chemistry calculations and validated against experimental data. We here show how it is possible to refine the full dihedral-angle potential of the Amber RNA force field by using solution NMR data as well as stability of known structural motifs. The procedure can be used to mix multiple systems and heterogeneous experimental information and crucially depends on a regularization term chosen with a cross-validation procedure. By fitting corrections to the dihedral angles on the order of less than 1 kJ/mol per angle, it is possible to increase the stability of difficult-to-fold RNA tetraloops by more than 1 order of magnitude.
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