CIFDock: A novel CHARMM-based flexible receptor-flexible ligand docking protocol.

Docking studies play a critical role in the current workflow of drug discovery. However, limitations may often arise through factors including inadequate ligand sampling, a lack of protein flexibility, scoring function inadequacies (e.g.

Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by amyloid (Aβ) aggregation, hyperphosphorylated tau, neuroinflammation, and severe memory deficits. Reports that certain boronic compounds can reduce amyloid accumulation and neuroinflammation prompted us to compare trans-2-phenyl-vinyl-boronic-acid-MIDA-ester (TPVA) and trans-beta-styryl-boronic-acid (TBSA) as treatments of deficits in in vitro and in vivo models of AD. We hypothesized that these compounds would reduce neuropathological deficits in cell-culture and animal models of AD.

Modeling Boronic Acid Based Fluorescent Saccharide Sensors: Computational Investigation of d-Fructose Binding to Dimethylaminomethylphenylboronic Acid.

Designing organic saccharide sensors for use in aqueous solution is a nontrivial endeavor. Incorporation of hydrogen bonding groups on a sensor's receptor unit to target saccharides is an obvious strategy but not one that is likely to ensure analyte-receptor interactions over analyte-solvent or receptor-solvent interactions. Phenylboronic acids are known to reversibly and covalently bind saccharides (diols in general) with highly selective affinity in aqueous solution.

Monosubstituted Phenylboronic Acids, R-B(OH) (R = CH, CHCH, CHNH, CHOH, and CHF): A Computational Investigation.

Phenylboronic acids (PBAs) are an important class of compounds with diverse applications in synthetic, biological, medicinal, and materials chemistry. In this investigation we report structural and thermochemical parameters for several monosubstituted , , and PBAs, R-B(OH) (R = CH, CHCH, CHNH, CHOH, and CHF). Equilibrium geometries of all the PBAs discussed in this article were obtained using second-order Møller-Plesset perturbation theory (MP2) with the Dunning-Woon aug-cc-pVDZ basis set; heats of formation (HOF) were calculated at the Gaussian-3 (G3) level of theory.

Disaggregation is a Mechanism for Emission Turn-On of ortho-Aminomethylphenylboronic Acid-Based Saccharide Sensors.

ortho-Aminomethylphenylboronic acid-based receptors with appended fluorophores are commonly used as molecular sensors for saccharides in aqueous media. The mechanism for fluorescence modulation in these sensors has been attributed to some form of photoinduced electron transfer (PET) quenching, which is diminished in the presence of saccharides. Using a well-known boronic acid-based saccharide sensor (3), this work reveals a new mechanism for fluorescence turn-on in these types of sensors.

Elucidating a chemical defense mechanism of Antarctic sponges: A computational study.

In 2000, a novel secondary metabolite (erebusinone, Ereb) was isolated from the Antarctic sea sponge, Isodictya erinacea. The bioactivity of Ereb was investigated, and it was found to inhibit molting when fed to the arthropod species Orchomene plebs. Xanthurenic acid (XA) is a known endogenous molt regulator present in arthropods.

A Comparison of the Structure and Bonding in the Aliphatic Boronic R-B(OH) and Borinic R-BH(OH) acids (R=H; NH, OH, and F): A Computational Investigation.

Boronic acids, R-B(OH), play an important role in synthetic, biological, medicinal, and materials chemistry. This investigation compares the structure and bonding surrounding the boron atoms in the simple aliphatic boronic acids, R-B(OH) (R = H; NH, OH, and F) and the analogous borinic acids, R-BH(OH). Geometry optimizations were performed using second-order Møller-Plesset perturbation theory (MP2) with the Dunning-Woon aug-cc-pVTZ, aug-cc-pVQZ and aug-cc-pV5Z basis sets; single-point CCSD(FC)/aug-cc-pVTZ//MP2(FC)/aug-cc-pVTZ level calculations were used to generate a QCI density for Natural Bond Orbital analyses of the bonding.

Heats of Formation for the Boronic Acids R-B(OH) and Boroxines RBO (R=H, Li, HBe, HB, HC, HN, HO, F, and Cl) Calculated at the G2, G3, and G4 Levels of Theory.

Boronic acids (R-B(OH)) and their boroxine (RBO) dehydration products have emerged as important classes of compounds with a multitude of diverse applications. However, the available heats of formation for these compounds are not always as accurate as would be required for further use. In this study the heats of formation at 298.

Comparison of Three Chain-of-States Methods: Nudged Elastic Band and Replica Path with Restraints or Constraints.

Chain-of-state methods are becoming important tools in studying the chemical reaction mechanisms, especially for biomacromolecules. In this article, three chain-of-state methods, nudged elastic band (NEB) method and the replica path method with restraints or constraints, were tested and compared using three model systems with various sizes and at different levels of theory: alanine dipeptide isomerization, β-alanine intramolecular condensation, and the matrix metalloproteinase 2 inhibition mechanism. The levels of theory used to describe the three model systems include molecular mechanics (MM), quantum mechanics (QM), and combined quantum mechanics and molecular mechanics (QM/MM).

MSCALE: A General Utility for Multiscale Modeling.

The combination of theoretical models of macromolecules that exist at different spatial and temporal scales has become increasingly important for addressing complex biochemical problems. This work describes the extension of concurrent multiscale approaches, introduces a general framework for carrying out calculations, and describes its implementation into the CHARMM macromolecular modeling package. This functionality, termed MSCALE, generalizes both the additive and subtractive multiscale scheme (e.

Thermodynamics of boroxine formation from the aliphatic boronic acid monomers R-B(OH)2 (R = H, H3C, H2N, HO, and F): a computational investigation.

Boroxines are the six-membered cyclotrimeric dehydration products of organoboronic acids, 3R–B(OH)2 → R3B3O3 + 3H2O, and in recent years have emerged as a useful class of organoboron molecules with applications in organic synthesis both as reagents and catalysts, as structural components in boronic-acid-derived pharmaceutical agents, and as anion acceptors and electrolyte additives for battery materials [Korich, A. L.; Iovine, P.

Efficient Calculation of QM/MM Frequencies with the Mobile Block Hessian.

The calculation of the analytical second derivative matrix (Hessian) is the bottleneck for vibrational analysis in QM/MM systems when an electrostatic embedding scheme is employed. Even with a small number of QM atoms in the system, the presence of MM atoms increases the computational cost dramatically: the long-range Coulomb interactions require that additional coupled perturbed self-consistent field (CPSCF) equations need to be solved for each MM atom displacement. This paper presents an extension to the Mobile Block Hessian (MBH) formalism for QM/MM calculations with blocks in the MM region and its implementation in a parallel version of the Q-Chem/CHARMM interface.

A computational investigation of the nitrogen-boron interaction in o-(N,N-dialkylaminomethyl)arylboronate systems.

o-(N,N-Dialkylaminomethyl)arylboronate systems are an important class of compounds in diol-sensor development. We report results from a computational investigation of fourteen o-(N,N-dialkylaminomethyl)arylboronates using second-order Møller-Plesset (MP2) perturbation theory. Geometry optimizations were performed at the MP2/cc-pVDZ level and followed by single-point calculations at the MP2/aug-cc-pVDZ(cc-pVTZ) levels.

Computational investigation of the oxidative deboronation of boroglycine, H2N-CH2-B(OH)2, Using H2O and H2O2.

We report results from a computational investigation of the oxidative deboronation of boroglycine, H2N-CH2-B(OH)2, using H2O and H2O2 as the reactive oxygen species (ROS) to yield aminomethanol, H2N-CH2-OH; these results complement our study on the protodeboronation of boroglycine to produce methylamine, H2N-CH3 (Larkin et al. J. Phys.

A computational characterization of boron-oxygen multiple bonding in HN=CH-CH=CH-NH-BO.

Structures, relative energies, and bonding characteristics for various conformers of 3-imino-N-(oxoboryl)prop-1-en-1-amine, HN=CH-CH=CH-NH-BO, and the corresponding borocycle (-HN=CH-CH=CH-NH-B-)O are discussed using results from second-order Møller-Plesset (MP2) perturbation theory with the Dunning-Woon correlation-consistent cc-pVDZ, aug-cc-pVDZ, and cc-pVTZ basis sets. These MP2 results are compared to those from computationally efficient density functional theory (DFT) calculations using the LDA, PBE, TPSS, BLYP, B3LYP, BVP86, OLYP, O3LYP, and PBE1PBE functionals in conjunction with the economical Pople-type 6-311++G(d,p) basis set to evaluate the suitability of these DFT/6-311++G(d,p) levels for use with larger boron-containing systems. The effects of an aqueous environment were incorporated into the calculations using COSMO methodology.

Dimers of boroglycine and methylamine boronic acid: a computational comparison of the relative importance of dative versus hydrogen bonding.

Boronic acids are widely used in materials science, pharmacology, and the synthesis of biologically active compounds. In this Article, geometrical structures and relative energies of dimers of boroglycine, H2N-CH2-B(OH)2, and its constitutional isomer H3C-NH-B(OH)2, were computed using second-order Møller-Plesset perturbation theory and density functional theory; Dunning-Woon correlation-consistent cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ basis sets were employed for the MP2 calculations, and the Pople 6-311++G(d,p) basis set was employed for a majority of the DFT calculations. Effects of an aqueous environment were incorporated into the results using PCM and COSMO-RS methodology.

A computational investigation of the geometrical structure and protodeboronation of boroglycine, H2N-CH2-B(OH)2.

In this article the geometrical structure of the simple, achiral, alpha-amino boronic acid boroglycine, H2N-CH2-B(OH)2, was investigated using density functional theory (DFT), second-order Møller-Plesset (MP2) perturbation theory, and coupled cluster methodology with single- and double-excitations (CCSD); the effects of an aqueous environment were incorporated into the results by using a few explicit water molecules and/or self-consistent reaction field (SCRF) calculations with the IEF polarizable continuum model (PCM). Neutral reaction mechanisms were investigated for the direct protodeboronation (hydrolysis) of boroglycine (H2O+H2N-CH2-B(OH)2-->B(OH)3+H2N-CH3), for which DeltaH degrees 298 was -21.9 kcal/mol at the MP2(FC)/aug-cc-pVDZ level, and for the 1,2-carbon-to-nitrogen shift of the -B(OH)2 moiety (H2N-CH2-B(OH)2-->H3C-NH-B(OH)2), for which the corresponding value of DeltaH degrees 298 was -18.

Hydrogen bridging in the compounds X2H (X=Al,Si,P,S).

X2H hydrides (X=Al, Si, P, and S) have been investigated using coupled cluster theory with single, double, and triple excitations, the latter incorporated as a perturbative correction [CCSD(T)]. These were performed utilizing a series of correlation-consistent basis sets augmented with diffuse functions (aug-cc-pVXZ, X=D, T, and Q). Al2H and Si2H are determined to have H-bridged C2v structures in their ground states: the Al2H ground state is of 2B1 symmetry with an Al-H-Al angle of 87.

Structure of the boronic acid dimer and the relative stabilities of its conformers.

Despite the widespread use of boronic acids in materials science and as pharmaceutical agents, many aspects of their structure and reactivity are not well understood. In this research the boronic acid dimer, [HB(OH)(2)](2), was studied by second-order Møller-Plesset (MP2) perturbation theory and coupled cluster methodology with single and double excitations (CCSD). Pople split-valence 6-31+G*, 6-311G**, and 6-311++G** and Dunning-Woon correlation-consistent cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ basis sets were employed for the calculations.

Assessing alkyl-, silyl-, and halo-substituent effects on the electron affinities of silyl radicals.

Neutral anion energy differences for a large class of alpha-substituted silyl radicals have been computed to determine the effect of alkyl, silyl, and halo substituents on their electron affinities. In particular, we report theoretical predictions of the adiabatic electron affinities (AEAs), vertical electron affinities (VEAs), and vertical detachment energies (VDEs) for a series of methyl-, silyl-, and halo-substituted silyl radical compounds. This work utilizes the carefully calibrated DZP++ basis set, in conjunction with the pure BLYP and OLYP functionals, as well as with the hybrid B3LYP, BHLYP, PBE1PBE, MPW1K, and O3LYP functionals.

The ability of silylenes to bind excess electrons: electron affinities of SiX(2), and SiXY species (X,Y=H,CH(3),SiH(3),F,Cl,Br).

Recently, Ishida and co-workers have isolated silylene radical anions via the one-electron reduction of isolable cyclic dialkylsilylenes, discovering these corresponding radical anions to be relatively stable at low temperatures. Herein we report theoretical predictions of the adiabatic electron affinities (AEA), vertical electron affinities, and vertical detachment energies of a series of methyl, silyl, and halosubstituted silylene compounds. This research utilizes the carefully calibrated DZP++ basis with the combination of the popular nonhybrid and hybrid DFT functionals, BLYP, B3LYP, and BHHLYP.