title: All-atom molecular dynamics analysis of multi-peptide systems reproduces peptide solubility in line with experimental observations.
abstract: In order to investigate the contribution of individual amino acids to protein and peptide solubility, we carried out 100 ns molecular dynamics (MD) simulations of 10(6) Å(3) cubic boxes containing ~3 × 10(4) water molecules and 27 tetra-peptides regularly positioned at 23 Å from each other and composed of a single amino acid type for all natural amino acids but cysteine and glycine. The calculations were performed using Amber with a standard force field on a special purpose MDGRAPE-3 computer, without introducing any "artificial" hydrophobic interactions. Tetra-peptides composed of I, V, L, M, N, Q, F, W, Y, and H formed large amorphous clusters, and those containing A, P, S, and T formed smaller ones. Tetra-peptides made of D, E, K, and R did not cluster at all. These observations correlated well with experimental solubility tendencies as well as hydrophobicity scales with correlation coefficients of 0.5 to > 0.9. Repulsive Coulomb interactions were dominant in ensuring high solubility, whereas both Coulomb and van der Waals (vdW) energies contributed to the aggregations of low solubility amino acids. Overall, this very first all-atom molecular dynamics simulation of a multi-peptide system appears to reproduce the basic properties of peptide solubility, essentially in line with experimental observations.
authors.affiliation: Department of Biotechnology and Life Sciences, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei-shi, Nakamachi, Tokyo 184-8588, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suenaga
authors.affiliation: Department of Biotechnology and Life Sciences, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei-shi, Nakamachi, Tokyo 184-8588, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Biotechnology and Life Sciences, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei-shi, Nakamachi, Tokyo 184-8588, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kosuda
authors.affiliation: Computational Biology Research Core, Quantitative Biology Center (QBiC), RIKEN, IMDA Building (6F), 1-6-5 Minatojima-Minami-machi, Chuo-ku, Kobe, Hyogo 630-0047, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Taiji
mesh_terms: D003198:Computer Simulation; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*
chemical_list: D010455:Peptides
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