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Scalable Moving-Domain QM/MM Methods

research figure 1Part of our research concerns the accurate description of electrostatic potentials in proteins and enzymes. The goal is to incorporate polarization effects in describing molecular interactions, providing first principles detail, and constructing efficient algorithms that scale linearly or quadratically with the size of the macromolecular system. We have developed the Moving-Domain QM/MM method to treat polarization effects in proteins. In addition, an open problem in modeling chemical events in QM/MM methods is how to incorporate solvent effects via continuum dielectric models. Considering that many chemical reactions of biological relevance take place near a liquid solution phase, an accurate theoretical treatment of such processes must incorporate a realistic description of environmental effects. We have been working on a scalable method based on a charge density fragmentation of a conductor-like screening model (DDF-COSMO), which can be incorporated into QM/MM and MOD-QM/MM.

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Polarization Effects in Protein Electrostatics

research figure 2Recent developments in the biophysical characterization of proteins have provided a means of directly measuring electrostatic fields by introducing a probe molecule to the system of interest and interpreting photon absorption in the context of the Stark effect. To fully account for this effect, the development of accurate atomistic models is of paramount importance. We have been exploring the application of polarization techniques to improve the description of electrostatic in the active site of proteins. This work has relevance in the computation of electric fields to aid the interpretation of Stark shift spectra in protein probes.

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Photochemistry of Carotenoid-containing Proteins

research figure3The orange carotenoid protein (OCP) is responsible for nonphotochemical quenching (NPQ) in cyanobacteria, a defense mechanism against potentially damaging effects of excess light conditions. This soluble two‐domain protein undergoes profound conformational changes upon photoactivation, involving translocation of the ketocarotenoid inside the cavity followed by domain separation. Domain separation is a critical step in the photocycle of OCP because it exposes the N‐terminal domain (NTD) to perform quenching of the phycobilisomes. Many details regarding the mechanism and energetics of OCP activation and domain separation remain unknown. We apply QM/MM methods and molecular dynamics to elucidate these events.

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Molecular Modeling of Monolayer Protected Gold Clusters

Our interest in computation and modeling of biomolecules extends also to the study of nano-materials. A variety of chemically tunable reactions in metallic nanoparticles can be obtained by encapsulation of nanocrystals in alkanethiolate monolayers to form hybrid systems known as monolayer protected clusters (MPCs). Exploiting MPCs for applications in the area of catalysis requires a proper structural and dynamical characterization of the physical properties of the protecting layer. In particular, we are interested in MPCs that can bio-conjugate with proteins.