The endoplasmic reticulum (ER)–mitochondrial encounter structure (ERMES) physically links the membranes of ER and mitochondria in yeast. Although cooperate to synthesize glycerophospholipids, whether ERMES directly facilitates lipid exchange between two organelles remains controversial. Here, we compared x-ray structures an subunit Mdm12 from Kluyveromyces lactis with that Saccharomyces cerevisiae found both proteins possess a hydrophobic pocket for phospholipid binding. However vitro...

Abstract In the context of drug design, C-H···O hydrogen bonds have received little attention so far, mostly because they are considered weak relative to other noncovalent interactions such as O-H···O bonds, π/π interactions, and van der Waals interactions. Herein, we demonstrate significance between C-H groups adjacent an ammonium cation oxygen atom (N + -C-H···O bonds) in protein-ligand complexes. Quantum chemical calculations revealed details on strength geometrical requirements these N a...

Abstract Exploration of the conformational spaces flexible biomacromolecules is essential for quantitatively understanding energetics their molecular recognition processes. We employed stable isotope‐ and lanthanide‐assisted NMR approaches in conjunction with replica‐exchange dynamics (REMD) simulations to obtain atomic descriptions high‐mannose‐type oligosaccharides, which harbor intracellular glycoprotein‐fate determinants triantennary structures. The experimentally validated REMD...

Abstract Antibody-dependent cellular cytotoxicity (ADCC) is promoted through interaction between the Fc region of immunoglobulin G1 (IgG1) and Fcγ receptor IIIa (FcγRIIIa), depending on N -glycosylation these glycoproteins. In particular, core fucosylation IgG1-Fc -glycans negatively affects this thereby compromises ADCC activity. To address mechanisms effect, we performed replica-exchange molecular dynamics simulations based crystallographic analysis a soluble form FcγRIIIa (sFcγRIIIa) in...

We propose a free energy calculation method for receptor-ligand binding, which have multiple binding poses that avoids exhaustive enumeration of the poses. For systems with poses, standard procedure is to enumerate orientations restrain ligand each orientation, and then, calculate energies pose. In this study, we modify part thermodynamic cycle in order sample broader conformational space site. This modification leads more accurate without performing separate simulations applied our simple...

Exchange of guest molecules into capsule shaped host is the most fundamental process in host−guest chemistry. Several examples quantitative measurements exchange rates have been reported. However, there no reports on activation energies these processes. A molecule known as cavitand−porphyrin (H2CP) has reported to a flexible structure capable facilitating moderate suitable for kinetic with 1H NMR. In this article, various and thermodynamic parameters related encapsulation small hydrocarbons...

We propose a conformational search method to find global minimum energy structure for protein systems. The simulated annealing is powerful local search. On the other hand, genetic crossover can space. Our incorporates these attractive features of and crossover. In previous works, we have been using Monte Carlo algorithm annealing. present work, use molecular dynamics instead. To examine effectiveness our method, compared results with those normal simulations by an α-helical miniprotein. used...

Abstract Exploration of the conformational spaces flexible biomacromolecules is essential for quantitatively understanding energetics their molecular recognition processes. We employed stable isotope‐ and lanthanide‐assisted NMR approaches in conjunction with replica‐exchange dynamics (REMD) simulations to obtain atomic descriptions high‐mannose‐type oligosaccharides, which harbor intracellular glycoprotein‐fate determinants triantennary structures. The experimentally validated REMD...

In Paper I of this series, the formulations optimization method existing force-field parameters for protein systems have been presented. We then applied it to five sets parameters, namely, AMBER parm94, parm96, parm99, CHARMM version 22, and OPLS-AA. order test validity these force fields, folding simulations α-helical β-hairpin peptides performed with each original optimized parameters. found that all modified gave both structures more consistent experimental implications than fields.

We optimized five existing sets of force-field parameters for protein systems by our recently proposed method. The force fields are AMBER parm94, parm96, parm99, CHARMM version 22, and OPLS-AA. method consists minimizing the sum square acting on each atom in proteins with structures from Protein Data Bank (PDB). selected partial-charge backbone torsion-energy this optimization, 100 molecules PDB were used. gave detailed comparisons found that there is a tendency convergence towards same...

We have previously proposed a method for refining force-field parameters of protein systems, which consists minimising the summation square force acting on each atom in proteins with structures from data bank (PDB). The results showed that modified all-atom model gave more consistent experimental implications than original fields. In this work, we applied and new to OPLS–UA field. method, perform minimisation average root-mean-square deviation various native structure. selected some...

We propose a new backbone-torsion-energy term in the force field for protein systems. This torsion-energy is represented by double Fourier series two variables, backbone dihedral angles phi and psi. It gives natural representation of torsion energy Ramachandran space sense that any two-dimensional surface periodic both psi can be expanded series. then easily control secondary-structure-forming tendencies modifying surface. For instance, we increase/decrease alpha-helix-forming-tendencies...

Many proteins carry out their biological functions by forming the characteristic tertiary structures. Therefore, search of stable states molecular simulations is important to understand and stabilities. However, getting state conformational difficult, because energy landscape system characterized many local minima separated high barriers. In order overcome this difficulty, various sampling optimization methods for conformations have been proposed. study, we propose a new method using genetic...

We performed folding simulations of three proteins using four force fields, AMBER parm96, parm99, CHARMM 27 and OPLS-AA/L, in order to examine the features these fields. studied proteins, protein A (all α-helix), cold-shock β-strand) G (α/β-structures), for simulations. For simulation, we used simulated annealing molecular dynamics method, which was 50 times each The results showed that secondary-structure-forming tendencies are largely different among parm96 favours β-bridge structures...

We examined a new backbone torsion-energy term proposed by us in the force field for protein systems. This is represented double Fourier series two variables, namely dihedral angles φ and ψ. It gives natural representation of torsion energy Ramachandran space sense that any two-dimensional surface periodic both ψ can be expanded series. then easily control secondary-structure-forming tendencies modifying surface. For instance, we increase or decrease α-helix-forming-tendencies lowering...

We propose a molecular simulation method using genetic algorithm (GA) for biomolecular systems to obtain ensemble averages efficiently. In this method, we incorporate the crossover, which is one of operations GA, any such as conventional dynamics (MD), Monte Carlo, and other methods. The crossover proposes candidate conformations by exchanging parts target molecule between pair during simulation. If are accepted, resumes from accepted ones. While simulations based on local update...

A cutinase-like enzyme (CLE), which is purified experimentally from the yeast Cryptococcus sp. strain S-2, has been recently found to degrade biodegradable plastics very efficiently. In this study,...

A peptide -m, which is a fragment from residue 21 to 31 of -microgloblin, experimentally known self-assemble and form amyloid fibrils. In order analyze the conformations amyloid-forming peptides in early stage aggregation, we applied replica-exchange molecular dynamics method system consisting three fragments -m. From analyses concerned with temperature dependence, found that there clear transition aggregate each other. Moreover, are two major stable states: One them like fibrils other...

We performed protein-ligand docking simulations with a ligand T247, which has been reported as selective inhibitor of histone deacetylase HDAC3, by the replica-exchange umbrella sampling method in order to estimate free energy profiles along pathways HDAC3-T247 and HDAC2-T247 systems. The simulation results showed that docked state system is more stable than although amino-acid sequences structures HDAC3 HDAC2 are very similar. By comparing obtained from both systems, we found difference...

We have reviewed chemoinformatics approaches for drug discovery such as aromatic interactions, clusters, structure generation, virtual screening, de novo design, evolutionary algorithm, inverse-QSPR/QSAR, Monte Carlo, molecular dynamics, fragment orbital method and matched pair analysis from the viewpoint of young researchers. intend to introduce various fields non-expert The this review is given follows: 1. Introduction, 2. Analysis Aromatic Interactions, 2.1 2.2 Clusters, 3. Ligand Based...

Many commonly used force fields for protein systems such as AMBER, CHARMM, GROMACS, OPLS, and ECEPP have amino-acid-independent force-field parameters main-chain torsion-energy terms. Here, we propose a new type of amino-acid-dependent terms in the fields. As an example, applied this approach to AMBER ff03 field determined ψ (N-Cα-C-N) ζ (Cβ-Cα-C-N) angles each amino acid by using our optimization method, which is one knowledge-based approach. In order test validity parameters, then...

We applied an effective conformational sampling method using genetic crossover to Trp-cage mini-protein. In this method, we incorporate the crossover, which is one of operations algorithm, in parallel molecular dynamics simulations. The can search global space by exchanging corresponding parts between a pair conformations protein. study, -helical protein, mini has 20 amino-acid residues. obtained from simulations are good agreement with experimental results.

We combined the genetic crossover, which is one of operations algorithm, and replica-exchange method in parallel molecular dynamics simulations. The crossover can search global conformational space by exchanging corresponding parts between a pair conformations protein. In this study, we applied to an $\alpha$-helical protein, Trp-cage mini has 20 amino-acid residues. obtained from simulations are good agreement with experimental results.