First-Principles-Based Multiscale, Multiparadigm Molecular Mechanics and Dynamics Methods for Describing Complex Chemical Processes

Abstract

We expect that systematic and seamless computational upscaling and downscaling for modeling, predicting, or optimizing material and system properties and behavior with atomistic resolution will eventually be sufficiently accurate and practical that it will transform the mode of development in the materials, chemical, catalysis, and Pharma industries. However, despite truly dramatic progress in methods, software, and hardware, this goal remains elusive, particularly for systems that exhibit inherently complex chemistry under normal or extreme conditions of temperature, pressure, radiation, and others. We describe here some of the significant progress towards solving these problems via a general multiscale, multiparadigm strategy based on first-principles quantum mechanics (QM), and the development of breakthrough methods for treating reaction processes, excited electronic states, and weak bonding effects on the conformational dynamics of large-scale molecular systems. These methods have resulted directly from filling in the physical and chemical gaps in existing theoretical and computational models, within the multiscale, multiparadigm strategy. To illustrate the procedure we demonstrate the application and transferability of such methods on an ample set of challenging problems that span multiple fields, system length- and timescales, and that lay beyond the realm of existing computational or, in some case, experimental approaches, including understanding the solvation effects on the reactivity of organic and organometallic structures, predicting transmembrane protein structures, understanding carbon nanotube nucleation and growth, understanding the effects of electronic excitations in materials subjected to extreme conditions of temperature and pressure, following the dynamics and energetics of long-term conformational evolution of DNA macromolecules, and predicting the long-term mechanisms involved in enhancing the mechanical response of polymer-based hydrogels.

Programmable siRNA pro-drugs that activate RNAi activity in response to specific cellular RNA biomarkers

“…We used atomistic molecular dynamics (MD) 28 , 29 , 30 , 31 , 32 to predict the 3D structures of two Cond-siRNA constructs incorporating some combinations of these modifications ( Figure 2 ; Table S2 ). MD shows that the constructs largely conformed to the design parameters.…”

Interaction of Natural Organic Matter with Layered Minerals: Recent Developments in Computational Methods at the Nanoscale

“…For the first of these challenges, the elements are there; research has been carried out on electron transfer processes in minerals, and more is understood regarding the nature and composition of NOM. The second challenge is presently limited to a few enhanced sampling MD methods [155,156]. Biased kinetic Monte Carlo methods can also be used to quickly search through a constrained set of possible reaction coordinates, though this technique has, hitherto, been mainly used to probe small molecules at catalyst surfaces [157].…”

Transient Changes in Molecular Geometries and How to Model Them

“…Therefore, Warshel & Levitt combined the QM and MM descriptions, choosing a chemically active region to be quantum mechanically described, while the rest of the system (coupled to the QM part) is described classically. This idea was quickly built upon, and numerous variations have been developed and implemented [154,155,156,157]. Ultimately, Warshel & Levitt, was together with Martin Karplus awarded the Nobel prize in chemistry in 2013 [158].…”