The crystal structure of photosystem II (PSII) analyzed at a resolution 1.9 Å revealed remarkably short H-bond between redox-active tyrosine Y(Z) and D1-His190 (2.46 donor-acceptor distance). Using large-scale quantum mechanical/molecular mechanical (QM/MM) calculations with the explicit PSII protein environment, we were able to reproduce this in original geometry neutral [Y(Z)O···H···N(ε)-His-N(δ)H···O═Asn] state, but not oxidized states, indicating that state was one observed structure. In...

The reaction mechanism of serine proteases (trypsin), which catalyze peptide hydrolysis, is studied theoretically by ab initio QM/MM electronic structure calculations combined with Molecular Dynamics−Free Energy Perturbation calculations. We have calculated the entire free energy profiles first step this enzyme (acylation process). present show that rate-determining acylation formation tetrahedral intermediate, and breakdown intermediate has a small barrier. activation for ∼17.8 kcal/mol at...

The fragment molecular orbital method (FMO) has been generalized to allow for multilayer structure. Fragments are assigned layers, and each layer can be described with a different basis set and/or level of electron correlation. Interlayer boundaries treated in the general spirit FMO since they also coincide some interfragment boundaries. question one- two-layer accuracy dependence upon fragmentation scheme is addressed. new applied predict reaction barrier heat Diels−Alder representative...

The fragment molecular orbital method (FMO) has been used with a large number of wave functions for single-point calculations, and its high accuracy in comparison to ab initio methods well established. We have developed the analytic derivative electrostatic interaction between far separated fragments performed restricted Hartree−Fock (RHF) geometry optimizations using FMO methods. In particular, α-helix, β-turn, extended conformers 10-residue polyalanine were studied good was established...

The reaction center chlorophylls a (Chla) of photosystem II (PSII) are composed six Chla molecules including the special pair PD1/PD2 harbored by D1/D2 heterodimer. They serve as ultimate electron abstractors for water oxidation in oxygen-evolving Mn4CaO5 cluster. Using PSII crystal structure analyzed at 1.9 Å resolution, redox potentials one-electron (Em) were calculated considering all subunits and protonation pattern titratable residues. Em(Chla) values to be 1015–1132 mV PD1 1141–1201...

Abstract The three‐body energy expansion in the fragment molecular orbital method (FMO) was applied to 2nd order Møller–Plesset theory (MP2). accuracy of both two and expansions determined for water clusters, alanine n ‐mers (α‐helices β‐strands) one synthetic protein, using 6‐31G* 6‐311G* basis sets. At best level (three‐body, molecules/residues per fragment), absolute errors relative ab initio MP2 were at most 1.2 5.0 mhartree, sets, respectively. worst 99.996% 99.96%, 6‐311G*, A...

Abstract The effect of solvation on the electronic structure ubiqutin protein was analyzed using ab initio fragment molecular orbital (FMO) method. FMO calculations were performed for in vacuo , and immersed an explicit solvent shell as thick 12 Å at HF or MP2 level by 6‐31G* basis set. protein's physical properties examined net charge, dipole moment, internal energy, interaction energy. Comparison computational results revealed following changes upon solvation. First, positively charged...

Thermal storage, a technology that enables us to control thermal energy, makes it possible reuse huge amount of waste heat, and materials with the ability treat larger energy are in high demand for energy-saving societies. Sugar alcohols now one promising candidate phase change (PCMs) because their large storage density. In this study, we computationally design experimentally unknown non-natural sugar predict density as basic step toward development new performance PCMs. The alcohol...

Sugar alcohols are one promising candidate for phase-change materials (PCMs) in energy industrial societies because of their large thermal storage capacity. In this paper, we investigate the melting point and enthalpy fusion related to six-carbon sugar (galactitol, mannitol, sorbitol, iditol) by molecular dynamics simulations elucidate physical principles required new PCM design. The computational points enthalpies reproduce experimental trend qualitatively. On basis decomposition analysis...

To elucidate the catalytic advantage of low-barrier hydrogen bond (LBHB), we analyze bonding network triad (His57-Asp102-Ser195) serine protease trypsin, one best examples LBHB reaction mechanism. Especially, focus on correlation between change chemical shifts and structural rearrangement active site in acylation process. clarify LBHB, evaluate two complementary properties. First, calculate NMR imidazole ring His57 by gauge-including atomic orbital (GIAO) approach within ab initio QM/MM...

The role of Asp102 in the catalytic relay system serine proteases is studied theoretically by calculating free energy profiles single proton-transfer reaction Asn102 mutant trypsin and concerted double (so-called charge-relay mechanism) wild-type trypsin. For each reaction, profile rate-determining step (the tetrahedral intermediate formation step) calculated using ab initio QM/MM electronic structure calculations combined with molecular dynamics−free perturbation method. In monotonically...

To elucidate the catalytic power of enzymes, we analyzed reaction profile Claisen rearrangement Bacillus subtilis chorismate mutase (BsCM) by all electron quantum chemical calculations using fragment molecular orbital (FMO) method. best our knowledge, this is first report ab initio-based entire enzyme system, where provide a detailed analysis factors that accomplish transition-state stabilization (TSS). FMO deliver an initio-level estimate intermolecular interaction between substrate and...

Assignment of particular roles to catalytic residues is an important requirement in clearly understanding enzyme functions. Therefore, predicting the activities mutant variants a fundamental challenge computational biochemistry. Although site-directed mutagenesis widely used for studying enzymatic and other classes protein function, interpreting mutation experiments usually difficult mainly due side effects induced by point mutations. Because steric and, many cases, electrostatic may affect...

Orotidine 5'-monophosphate decarboxylase (ODCase) accelerates the decarboxylation of orotidine (OMP) to uridine (UMP) by 17 orders magnitude. Eight new crystal structures with ligand analogues combined computational analyses enzyme's short-lived intermediates and intrinsic electronic energies distort substrate other ligands improve our understanding still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion its methyl...

The reaction mechanism of biomass decomposition by xylanases remains the subject debate. To clarify we investigated glycosylation step GH11 xylanase, an enzyme that catalyzes hydrolysis lignocellulosic hemicellulose (xylan). Making use a recent neutron crystal structure, which revealed protonation states relevant residues, used ab initio quantum mechanics/molecular mechanics (QM/MM) calculations to determine detailed step. In particular, our focus is on controversial question whether or not...

Abstract All electron calculations were performed on the photosynthetic reaction center of Blastochloris viridis , using fragment molecular orbital (FMO) method. The protein complex 20,581 atoms and 77,754 electrons was divided into 1398 fragments, two‐body expansion FMO/6‐31G* applied to calculate ground state. excited electronic states embedded transfer system separately calculated by configuration interaction singles approach with multilayer FMO Despite structural symmetry system,...

In this study, we investigated the electronic character of protein environment in enzymatic processes by performing all-electron QM calculations based on fragment molecular orbital (FMO) method. By introducing a new computational strategy combining analysis with ab initio QM/MM modeling, details interaction energy between reactive substrate and amino acid residues at catalytic site. For practical application, selected chorismate mutase catalyzed reaction as an example. Because time required...

To advance our knowledge of carbohydrate recognition by lectins, we propose a systematic computational modeling strategy to identify complex sugar-chain conformations on the reduced free energy surface (FES). We selected E-selectin with sialyl Lewis X (denoted E-selectin/SLe(x) complex) as first target molecule. First, introduced 2D-FES that characterizes conformational changes in structure well degree solvation stability ligand, and evaluated overall profile classical molecular dynamics...

A full electron calculation for the photosynthetic reaction center of Rhodopseudomonas viridis was performed by using fragment molecular orbital (FMO) method on a massive cluster computer. The target system contains 20,581 atoms and 77,754 electrons, which divided into 1,398 fragments. According to FMO prescription, calculations fragments pairs were conducted obtain electronic state system. at RHF/6-31G* level theory took 72.5 hours with 600 CPUs. CPUs grouped several workers, dispatched. An...

A uridine-cytidine kinase (UCK) catalyzes the phosphorylation of uridine (Urd) and cytidine (Cyd) plays a significant role in pyrimidine-nucleotide salvage pathway. Unlike ordinary ones, UCK from Thermus thermophilus HB8 (ttCK) loses catalytic activity on Urd due to lack substrate binding ability possesses an unusual amino acid, i.e. tyrosine 93 (Tyr93) at site, whereas histidine (His) is located other UCKs. Mutagenesis experiments revealed that replacement Tyr93 by His or glutamine (Gln)...

Norovirus is a major pathogen of nonbacterial acute gastroenteritis in humans and animals. Carbohydrate recognition between norovirus capsid proteins Lewis antigens considered to play critical role initiating infection eukaryotic cells. In this article, we first report detailed atomistic simulation study the protein complex with antigen based on ab initio QM/MM combined MD-FEP simulations. To understand mechanistic details ligand binding, analyzed compared carbohydrate mechanism wild-type P...

Effective management of reusable waste heat is one the most important technologies for reducing energy consumption and promoting conservation. In particular, chemical storage a practical solution to spatial temporal mismatches use. Among various reactions, reversible hydration process periclase (MgO) brucite [Mg(OH)2] candidate future applications in social systems. this article, order clarify atomistic reaction mechanism thermochemical MgO reaction, we calculated potential profiles...

Objective: The purpose of this study was to investigate the effects prolonged (24-h) non-acidemic hypoxemia on plasma endothelin-1 and atrial natriuretic peptide (ANP) in fetal goats. Methods: During continuous infusion nitrogen into maternal trachea, ANP levels were measured nine chronically instrumented goat fetuses at 117-129 days' gestation. Endothelin-1 by radioimmunoassay. Results: Fetal arterial p O 2 decreased significantly from 23.1 &#45 1.0 mmHg (control) 15.2 0.9 during first h...