The aqueous environment as an active participant in the protein folding process

Existing computational models applied in the protein structure prediction process do not sufficiently account for the presence of the aqueous solvent. The solvent is usually represented by a predetermined number of H2O molecules in the bounding box which contains the target chain. The fuzzy oil drop (FOD) model, presented in this paper, follows an alternative approach, with the solvent assuming the form of a continuous external hydrophobic force field, with a Gaussian distribution. The effect of this force field is to guide hydrophobic residues towards the center of the protein body, while promoting exposure of hydrophilic residues on its surface. This work focuses on the following sample proteins: Engrailed homeodomain (RCSB: 1 enh), Chicken villin subdomain hp-35, n68h (RCSB: 1yrf), Chicken villin sub-domain hp-35, k65(nle), n68h, k70(nle) (RCSB: 2f4k), Thermostable subdomain from chicken villin headpiece (RCSB: 1vii), de novo designed single chain three-helix bundle (a3d) (RCSB: 2a3d), albumin-binding domain (RCSB: 1prb) and lambda repressor-operator complex (RCSB: 1lmb). (C) 2018 The Authors. Published by Elsevier Inc.