Molecular dynamics out of equilibrium: mechanics and measurables

Abstract

Molecular dynamics is fundamentally the integration of the equations of motion over a representation of an atomic and molecular system. The most rigorous choice for performing molecular dynamics entails the use of quantum-mechanical equations of motion and a representation of the molecular system through all of its electrons and atoms. For most molecular problems involving at least hundreds of atoms, but generally many more, this is simply computationally prohibitive. Thus the art of molecular dynamics lies in choosing the representation and the appropriate equations of motion capable of addressing the requisite measurables. When used adroitly, it can provide both equilibrium (averaged) and time-dependent properties of a molecular system. Many computational packages now exist that perform molecular dynamics simulations. They generally include force fields to represent the interactions between atoms and molecules (smoothing out electrons through the Born-Oppenheimer approximation) and integrate the remaining particles classically. Despite these simplifications, all-atom molecular dynamics remains computationally inaccessible if one includes the number of atoms required to simulate mesoscopic solvents. Here we use analytical models to demonstrate how molecular dynamics can be used to limit the solvent size in systems experiencing either equilibrium or nonequilibrium conditions. It is equally important to address the measurables (such as reaction rates) that are to be obtained prior to the generation of the data-intensive trajectories.

Peripheral Membrane Proteins Facilitate Nanoparticle Binding at Lipid Bilayer Interfaces

“…A challenge for characterizing nanoparticles and membrane proteins on bilayers using computational models lies in the simultaneous relevance of many length scales: those associated with the nanoparticle structure, the nanoparticle surface, the relative distances of the nanoparticle and protein to the bilayer, and the even larger lengths of the bilayer. In this work, we exploit the increasing power of computers to propagate all-atom MD simulations of relatively large systems at long times by focusing on the smaller system consisting of only a membrane protein and a bilayer surface to infer the possible points of contact to a nanoparticle.…”

“…A challenge for characterizing nanoparticles and membrane proteins on bilayers using computational models lies in the simultaneous relevance of many length scales: those associated with the nanoparticle structure, the nanoparticle surface, the relative distances of the nanoparticle and protein to the bilayer, and the even larger lengths of the bilayer. In this work, we exploit the increasing power of computers to propagate all-atom MD simulations of relatively large systems at long times 85 1 shows the adaptive Poisson−Boltzmann electrostatic potential of the cyt c surface in three orientations to highlight the nearly completely electropositive nature of face 1 and the mixture of positively and negatively charged regions on faces 2 and 3. Face 1 was chosen to direct the electropositive heme group toward the bilayer surface.…”

Adsorption Dynamics and Structure of Polycations on Citrate-Coated Gold Nanoparticles

“…Computer simulations can potentially link atomistic-scale interactions between nanoparticles and biomolecules to the onset of toxicity in cells, but require accurate bottom-up coarse-graining to tackle this inherently multiscale problem. , A common bottom-up coarse-graining strategy for complex multicomponent systems, such as nanoparticles in suspension media or in biological environments, starts with the atomistic structure of each component at the lowest scale and then groups neighboring atoms with similar chemical properties into larger beads at the higher scale. The MARTINI coarse-grained lipid model follows a similar approach and has been parameterized by Marrink and co-workers to obtain a force field that can reproduce the partitioning of polar and apolar phases across a broad class of amphiphilic molecules.…”

A Cuban Campesino in Chemistry’s Academic Court

“…We also examined the nontrivial dynamics of energy landscapes with multiple deep funnels and found evidence that some frustration could be an important driver in protein funding . In recent years, Chem-DiCE has become more mainstream, though it has been narrowed a bit to include mostly ultrafast and related phenomenon. − I invite all of us to think differently and once again reimagine the need to resolve Chem-DiCE as part of this century’s grand challenge to resolve space and time across multiple chemical scales simultaneously …”

“…47−49 I invite all of us to think differently and once again reimagine the need to resolve Chem-DiCE as part of this century's grand challenge to resolve space and time across multiple chemical scales simultaneously. 50 The Nobel Prize, well earned by Levitt, Karplus, and Warshell in 2013, cited them "for the development of multiscale models for complex chemical systems." 51 Together with the tools that followed, 52−56 this has led to many advances in molecular simulations, including the recent signature achievement by Rommie Amaro and her co-workers demonstrating the structure of the spike protein using all-atom MD.…”