Water–Peptide Dynamics during Conformational Transitions

Abstract

Transitions between metastable conformations of a dipeptide are investigated using classical molecular dynamics simulation with explicit water molecules. The distribution of the surrounding water at different moments before the transitions and the dynamical correlations of water with the peptide's configurational motions indicate that the water molecules represent an integral part of the molecular system during the conformational changes, in contrast with the metastable periods when water and peptide dynamics are essentially decoupled. SECTION:Liquids; Chemical and Dynamical Processes in Solution R ecent investigations of protein dynamics indicate that water plays the major role in protein motion. Indeed, there is a large body of experimental and simulation evidence 1−9 showing a close connection between the water dynamics and the protein conformations. Frauenfelder and colleagues have experimentally shown that protein-dominant conformational motions are slaved by the hydration shell and the bulk solvent, 10 whereas the protein molecule itself provides an "active matrix" necessary for guiding the water's dynamics toward biologically relevant conformational changes. The change in water dynamics at the shell of up to almost a dozen water molecule diameters around proteins is found in ref 11. Very recently, a neutron scattering study demonstrated that the interfacial (hydration) water is the main "driving force" of protein dynamics governing both local and large scale motions in proteins. 12 Finally, the critical role of solvating water has been demonstrated for an important applied field of protein− ligand binding. 13 Despite extensive research on protein dynamics, the investigations of elementary conformational motions are rare. The knowledge of specific molecular mechanisms, including the role of water molecules that drive the conformational moves, is highly demanded because these elementary conformational changes ultimately define all rearrangements of proteins as a whole.In this work, we analyze molecular dynamics (MD) simulated peptide focusing on the moments of elementary conformational changes including explicit water molecules. We show that water indeed drives the changes and we elucidate the specific mechanisms of this phenomenon.We study a zwitterion L-alanyl-L-alanine, Figure 1. This is a very convenient model because (i) the conformation of the molecule is completely defined by the two dihedral angles ψ and ϕ; (ii) in water the conformation ψ ≈ 2.5, ϕ ≈ −2.2 radians is prevalent, however, very rare transitions to two other metastable conformations (ψ ≈ −1, ϕ ≈ −2.2 and ψ ≈ 2.5, ϕ ≈ 1) take place, and (iii) the transitions only happen in water because in vacuum the negatively charged COO − group strongly interacts with the positively charged NH 3 + group, excluding all conformations except the one with the groups at the minimal distance from each other.Two different MD models of the system (see the Supporting Information) have been studied. One is the united atom forcefield GROMOS, 14 the othe...

All-Atom Molecular Dynamics Simulations of Entire Virus Capsid Reveal the Role of Ion Distribution in Capsid’s Stability

“…This is because, as commonly agreed, the hydration water is the main “driving force” of protein dynamics governing both local and large scale motions in proteins. 26 …”

Concurrent multiscale modelling of atomistic and hydrodynamic processes in liquids

“…The correlations are very strong in the first hydration shell of the biomolecule and remain non-negligible at a significant distance from it. Moreover, as we have shown [14], these correlations are qualitatively different in various regimes of the peptide's dynamics: they are strong at the moments of conformational transitions (when the shape of the peptide changes significantly) and weak at the times of metastable fluctuations of the peptide around the same average shape. Thus, the microscopic fluctuations not only are non-negligible, but also constitute the essence of the molecular phenomenon.…”

Multiscale molecular dynamics/hydrodynamics implementation of two dimensional “Mercedes Benz” water model

“…It is now commonly recognised that surrounding solvent molecules play an important role in the process of protein folding [6]. Recent investigations demonstrate the connection between the water molecules dynamics in the vicinity of proteins and protein conformational motion [7]. According to the study, protein chains are guided by the water hydration shell at the periods of major conformational rearrangements.…”