Thomas F. Miller

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We present a coarse-grained modeling approach that spans the nanosecond- to minute-timescale dynamics of cotranslational protein translocation. The method enables direct simulation of both integral membrane protein topogenesis and transmembrane domain (TM) stop-transfer efficiency. Simulations reveal multiple kinetic pathways for protein integration,(More)
Density functional theory (DFT) provides a formally exact framework for quantum embedding. The appearance of nonadditive kinetic energy contributions in this context poses significant challenges, but using optimized effective potential (OEP) methods, various groups have devised DFT-in-DFT methods that are equivalent to Kohn−Sham (KS) theory on the whole(More)
The most widely used algorithm for Monte Carlo sampling of electronic transitions in trajectory surface hopping (TSH) calculations is the so-called anteater algorithm, which is inefficient for sampling low-probability nonadiabatic events. We present a new sampling scheme (called the army ants algorithm) for carrying out TSH calculations that is applicable(More)
Embedded density functional theory (e-DFT) is used to describe the electronic structure of strongly interacting molecular subsystems. We present a general implementation of the Exact Embedding (EE) method [J. Chem. Phys. 133, 084103 (2010)] to calculate the large contributions of the nonadditive kinetic potential (NAKP) in such applications. Potential(More)
We have used the ring polymer molecular-dynamics method to study the translational and orientational motions in an extended simple point charge model of liquid water under ambient conditions. We find, in agreement with previous studies, that quantum-mechanical effects increase the self-diffusion coefficient D and decrease the relaxation times around the(More)
We combine path-integral Monte Carlo methods with high-quality potential energy surfaces to compute equilibrium isotope effects in a variety of systems relevant to 'clumped' isotope analysis and isotope geochemistry, including CO2, N2O, methane, and propane. Through a systematic study of heavy-atom isotope-exchange reactions, we quantify and analyze errors(More)
Sliding clamps are toroidal proteins that encircle DNA and act as mobile platforms for DNA replication and repair machinery. To be loaded onto DNA, the eukaryotic sliding clamp Proliferating Cell Nuclear Antigen (PCNA) must be splayed open at one of the subunit-subunit interfaces by the ATP-dependent clamp loader, Replication Factor C, whose(More)
We analyze the sources of error in quantum embedding calculations in which an active subsystem is treated using wavefunction methods, and the remainder using density functional theory. We show that the embedding potential felt by the electrons in the active subsystem makes only a small contribution to the error of the method, whereas the error in the(More)
We characterize the conformational dynamics and substrate selectivity of the signal recognition particle (SRP) using a thermodynamic free energy cycle approach and microsecond timescale molecular dynamics simulations. The SRP is a central component of the co-translational protein targeting machinery that binds to the N-terminal signal peptide (SP) of(More)
The canonical mechanism for multispanning membrane protein topogenesis suggests that protein topology is established during cotranslational membrane integration. However, this mechanism is inconsistent with the behavior of EmrE, a dual-topology protein for which the mutation of positively charged loop residues, even close to the C-terminus, leads to(More)