Conformational Entropy as Collective Variable for Proteins
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† Department of Chemistry and Applied Biosciences, ETH Zurich c/o USI Campus, Via Giuseppe Buffi 13, CH-6900, Lugano, Switzerland
‡ Facoltà di Informatica, Instituto di Scienze Computationali, Università della Svizzera italiana, Via Giuseppe Buffi 13, CH-6900, Lugano, Switzerland
§ National Center for Computational Design and Discovery of Novel Materials MARVEL, Università della Svizzera italiana, Via Giuseppe Buffi 13, CH-6900, Lugano, Switzerland
*E-mail: [email protected]
Abstract
Many enhanced sampling methods rely on the identification of appropriate collective variables. For proteins, even small ones, finding appropriate descriptors has proven challenging. Here we suggest that the NMR S2 order parameter can be used to this effect. We trace the validity of this statement to the suggested relation between S2 and conformational entropy. Using the S2 order parameter and a surrogate for the protein enthalpy in conjunction with metadynamics or variationally enhanced sampling, we are able to reversibly fold and unfold a small protein and draw its free energy at a fraction of the time that is needed in unbiased simulations. We also use S2 in combination with the free energy flooding method to compute the unfolding rate of this peptide. We repeat this calculation at different temperatures to obtain the unfolding activation energy.
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