Real time dynamical properties of biomolecules from ab initio quantum dynamics
Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
Final Report Abstract
The inclusion of nuclear quantum effects (NQE) in the evaluation of real-time dynamical observables from computer simulations is a standing challenge, especially in the realm of ab initio electronic structure calculations of realistic materials and molecules. In this project, I have developed new theoretical methods to include NQE in dynamical quantities, and applied it to systems of biological relevance. With respect to methodological developments, we have proposed a new method to approximate quantum contributions in time-dependent properties based on a path integral framework, called thermostatted ring polymer molecular dynamics (TRPMD). This method is immune to pathological problems of and more efficient than previously proposed methods, still retaining all mathematical limits that could be proven for ring polymer molecular dynamics (RPMD). In the absence of reliable benchmarks for quantum dynamics of condensed phase systems (that can also be of biological relevance), we have assessed the performance of TRPMD by carrying systematic comparisons of the predicted IR spectrum of HOD in D2O and water with other approaches that rely on different approximations to quantum dynamics. We found that the different techniques are largely consistent with one another, within a few tens of cm−1 . Comparison with classical molecular dynamics demonstrates the importance of NQE even up to 600K. The cross validation between these different approaches provided us with clues to limitations of their underlying approximations and relevant information in order to develop more reliable approaches to nuclear quantum dynamics that are feasible together with electronic structure methods. Regarding applications, we have treated at first isolated biomolecules. These systems are especially challenging since they are stabilized by a delicate balance of weak interactions, making it important to assess all energetic contributions in an accurate manner. We examined stacked polyglutamine (polyQ) strands, a peptide repeat often found in amyloid aggregates. We investigated the role of hydrogen bond (HB) cooperativity, van der Waals (vdW) dispersion interactions, and quantum contributions to free energies, including anharmonicities through density functional theory and ab initio path integral simulations. Of these various factors, we find that the largest impact on structural stabilization comes from vdW interactions. HB cooperativity is the second largest contribution as the size of the stacked chain grows. Competing nuclear quantum effects make the net quantum contribution small but very sensitive to anharmonicities, vdW, and the number of HBs. We find that there are strong quantum anharmonicities on the CH, NH, and OH stretch regions for these molecules. Finally, as an application that directly profits from the TRPMD method, we have studied the diffusion of protons and hydroxide ions through water wires. In biological environments, water wires are often the conducting medium for protons or hydroxide ions in channels, involved in a variety of biological processes that deal with the control of pH and charge concentration gradients. We have assessed the impact of NQE in these diffusion processes by treating isolated water wires of different lengths in a first principles electronic structure potential energy surface. We used machine learning techniques to identify the charged species and calculated diffusion coefficients with ab initio molecular dynamics (classical nuclei) and ab initio TRPMD. We propose models to eliminate finite size effects and estimate diffusion coefficients, finding indications that nuclear quantum effects play a role depending on the predicted water-water separation, and is more accentuated for the hydroxide ions.
Publications
- Communication: On the Consistency of Approximate Quantum Dynamics Simulation Methods for Vibrational Spectra in the Condensed Phase, J. Chem. Phys. 141, 181101 (2014)
M. Rossi, H. Liu, F. Paesani, J. Bowman, M. Ceriotti
(See online at https://doi.org/10.1063/1.4901214) - How to remove the spurious resonances from ring polymer molecular dynamics, J. Chem. Phys. 140, 234116 (2014)
M. Rossi, M. Ceriotti, D. Manolopoulos
(See online at https://doi.org/10.1063/1.4883861) - Going Clean: Structure and Dynamics of Peptides in the Gas Phase and Paths to Solvation, J. Phys.: Cond. Mat. 27, 493002 (2015)
C. Baldauf and M. Rossi
(See online at https://doi.org/10.1088/0953-8984/27/49/493002) - Stability of Complex Biomolecular Structures: Van der Waals, Hydrogen Bond Cooperativity, and Nuclear Quantum Effects, J. Phys. Chem. Lett. 6, 4233 (2015)
M. Rossi, W. Fang, A. Michaelides
(See online at https://doi.org/10.1021/acs.jpclett.5b01899)
