Read by QxMD icon Read

Molecular dynamics simulation free energy

Neha Singh, Vikram Dalal, Pravindra Kumar
Human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (hACMSD) is a zinc containing amidohydrolase which is a vital enzyme of the kynurenine pathway in tryptophan metabolism. It prevents the accumulation of quinolinic acid (QA) and helps in the maintenance of basal trp-niacin ratio. To assess the structure based inhibitory action of PAEs such as DMP, DEP, DBP, DIBP, DEHP and their metabolites, these were docked into the active site cavity of hACMSD. Docking results show that the binding affinities of PAEs lie in the comparable range (-4...
December 4, 2017: International Journal of Biological Macromolecules
Farshid Zargari, Maryam Lotfi, Omolbanin Shahraki, Zahra Nikfarjam, Jafar Shahraki
Protein tyrosine phosphatase 1B (PTP1B) is a member of the PTP superfamily which is considered to be a negative regulator of insulin receptor (IR) signalling pathway. PTP1B is a promising drug target for the treatment of type 2 diabetes, obesity and cancer. The existence of allosteric site in PTP1B has turned the researcher's attention to an alternate strategy for inhibition of this enzyme. Herein, the molecular interactions between the allosteric site of PTP1B with three non-competitive flavonoids, (MOR), (MOK), and (DPO) have been investigated...
December 7, 2017: Journal of Biomolecular Structure & Dynamics
Alireza Nemati, Hossein Nejat Pishkenari, Ali Meghdari, Saeed Sohrabpour
A new method for guiding the motion of fullerene and fullerene-based nanocars is introduced in this paper. The effects of non-flat substrates on the motion of C60, a nanocar and a nanotruck are investigated at different conditions and temperatures. Their behavior is studied using two different approaches: analyzing the variation in potential energy and conducting all-atom classical molecular dynamics simulations. This paper proposes that the use of a stepped substrate will make their motion more predictable and controllable...
December 6, 2017: Physical Chemistry Chemical Physics: PCCP
Toru Ekimoto, Mitsunori Ikeguchi
Protein functions require specific structures frequently coupled with conformational changes. The scale of the structural dynamics of proteins spans from the atomic to the molecular level. Theoretically, all-atom molecular dynamics (MD) simulation is a powerful tool to investigate protein dynamics because the MD simulation is capable of capturing conformational changes obeying the intrinsically structural features. However, to study long-timescale dynamics, efficient sampling techniques and coarse-grained (CG) approaches coupled with all-atom MD simulations, termed multiscale MD simulations, are required to overcome the timescale limitation in all-atom MD simulations...
December 4, 2017: Biophysical Reviews
Danfeng Shi, Shuangyan Zhou, Xuewei Liu, Chenxi Zhao, Huanxiang Liu, Xiaojun Yao
BACKGROUND: The inhibitors blocking the interaction between programmed cell death protein 1(PD-1) and programmed death-ligand 1(PD-L1) can activate the immune response of T cell and eliminate cancer cells. The crystallographic studies have provided structural insights of the interactive interfaces between PD-L1 and its protein ligands. However, the hotspot residues on PD-L1 as well as structural and energetic basis for different protein ligands still need to be further investigated. METHODS: Molecular modeling methods including molecular dynamics simulation, per-residue free energy decomposition, virtual alanine scanning mutagenesis and residue-residue contact analysis were used to qualitatively and quantitatively analyze the interactions between PD-L1 and different protein ligands...
December 1, 2017: Biochimica et Biophysica Acta
Wudi Cao, Yanting Wang, Giacomo Saielli
We simulate the heating process of ionic liquids [CnMim][NO3] (n = 4, 6, 8, 10, 12), abbreviated as Cn, by means of molecular dynamics (MD) simulation starting from a manually constructed triclinic crystal structure composed of polar layers containing anions and cationic head groups and nonpolar regions in between containing cationic alkyl side chains. During the heating process starting from 200 K, each system undergoes first a solid-solid phase transition at a lower temperature, and then a melting phase transition at a higher temperature to an isotropic liquid state (C4, C6 and C8) or to a liquid crystal state (C10 and C12)...
December 4, 2017: Journal of Physical Chemistry. B
Dhanachandra Singh Khuraijam, Hamiyet Unal, Russell Desnoyer, Sadashiva S Karnik
Crystal structures of the human angiotensin II type 1 receptor (AT1R) complex with the anti-hypertensive agent ZD7155 (PDB id: 4YAY) and the blood pressure medication Benicar (PDB id: 4ZUD) showed that binding poses of both antagonists are similar. This finding implies that clinically used angiotensin receptor blocking (ARB) drugs may interact in a similar fashion. However, clinically observed differences in pharmacological and therapeutic efficacies of ARBs lead to the question whether the dynamic interactions of AT1R with ARBs vary? To address this, we performed induced-fit docking (IFD) of eight clinically used ARBs to AT1R followed by 200 nanosecond molecular dynamic (MD) simulation...
December 1, 2017: Journal of Chemical Information and Modeling
Marlet Martinez, Benjamin Garcia, Brenda Colin, M Bello, Berenice Prestegui, Alma Chavez, Alfonso Duenas, Jonathan Fragoso, Jessica Mendieta, Edgar Rojano, David Ordaz, Rocio Garcia, D Castillo-Bautista, Jose Correa
Estrogen (17β-estradiol) is essential for normal growth and differentiation in the mammary gland. Previous investigations have revealed that estrogen receptor alpha (ERα) plays a critical role in breast cancer. More recently, observations regarding the widespread expression of ERβ-like proteins in normal and neoplastic mammary tissues have suggested that ERβ is also involved in the mentioned pathology. Design of new drugs both steroidal and nonsteroidal that target any of these receptors represents a promise to treat breast cancer...
November 29, 2017: Anti-cancer Agents in Medicinal Chemistry
B Shadrack Jabes, Dusan Bratko, Alenka Luzar
Surface interactions between chemically-mixed surfaces, as well as those among dissolved biomolecules, comprise distinct contributions from polar and hydrophobic moieties. These contributions are often context dependent. Approximate compliance to the Cassie's additivity equation for the wetting free energies on mixed surfaces in water is, however, indicative of similarly additive forces between individual surface elements, suggesting a quadratic interpolation model for total force from the forces between pure surfaces...
November 29, 2017: Journal of Physical Chemistry. B
Antenor J Paulista Neto, Vitaly V Chaban, Eudes E Fileti
Hydration properties of graphene oxide (GO) are essential for most of its potential applications. In this work, we employ atomistic molecular dynamics simulations to investigate seven GO compositions with different levels of oxygenation. Two atomic charge models for GO are compared: (1, a simplified model) sp2 carbons are purely Lennard-Jones sites; (2, a CHELPG model) sp2 carbon charges are consistent with the CHELPG scheme. Structural properties were found to depend insignificantly on the charge model, whereas thermodynamics appeared very sensitive...
November 29, 2017: Physical Chemistry Chemical Physics: PCCP
Inderpal Singh, Shashank Singh, Vijeshwar Verma, Vladimir N Uversky, Ratna Chandra
Epidermal growth factor receptor (EGFR) kinase is implicated in cancer development due to either overexpression or activation variants in its functional intracellular kinase domain. Threonine to Methionine (Thr 790 Met) is one such variant observed commonly in patients showing resistance to kinase inhibitor drug Erlotinib. Two mechanisms for resistance have been proposed (1) steric hindrance and (2) enhanced binding to ATP. In this study, we employed molecular dynamics simulations and studied both the mechanisms...
November 28, 2017: Journal of Biomolecular Structure & Dynamics
Anna Cebrián-Prats, Tiffani Rovira, Patricia Saura, Àngels González-Lafont, José M Lluch
Ebselen is a potent competitive inhibitor of the active form of rabbit 15-lipoxygenase, an enzyme involved in many inflammatory diseases. Light induced Z-to-E isomerization of the ebselen-like 2-(3-benzylidene)-3-oxo-2,3-dihydrobenzo[b]thiophene-7-carboxylic acid methyl ester (BODTCM) molecule was used to convert the weak (Z)-BOTDCM inhibitor into the (E)-isomer with much higher inhibitory capacity. In this study, the binding modes of ebselen, (E)-BOTDCM and (Z)-BOTDCM have been analyzed to provide molecular insights on the inhibitory potency of ebselen and on the geometric-isomer specificity of (E)- and (Z)-BOTDCM inhibitors...
November 28, 2017: Journal of Physical Chemistry. A
Duy Phuoc Tran, Kazuhiro Takemura, Kazuo Kuwata, Akio Kitao
We investigated the dissociation process of tri-N-acetyl-D-glucosamine from hen egg white lysozyme using parallel cascade selection molecular dynamics (PaCS-MD), which comprises cycles of multiple unbiased MD simulations using a selection of MD snapshots as the initial structures for the next cycle. Dissociation was significantly accelerated by PaCS-MD, in which the probability of rare event occurrence toward dissociation was enhanced by the selection and re-randomization of the initial velocities. Although this complex was stable during 1 μs of conventional MD, PaCS-MD easily induced dissociation within 100 - 101 ns...
November 28, 2017: Journal of Chemical Theory and Computation
Ondrej Gutten, Daniel Bím, Jan Řezáč, Lubomir Rulisek
To find and calibrate a robust and reliable computational protocol for mapping conformational space of medium-sized molecules, exhaustive conformational sampling has been carried out for the series of seven macrocyclic compounds of varying ring size and one acyclic analogue. While five of them were taken from the MD/LLMOD/force-field study by Shelley and coworkers (J. Chem. Inf. MODEL: 2014, 54, 2680), three represent potential macrocyclic inhibitors of human cyclophilin A. The free energy values (GDFT/COSMO-RS) for all conformers of each compound were obtained by the composite protocol based on the in vacuo quantum mechanics (DFT-D3 method in a large basis set), standard gas-phase thermodynamics and the COSMO-RS solvation model (QM+COSMO-RS)...
November 28, 2017: Journal of Chemical Information and Modeling
Haley M Stowe, Gyeong S Hwang
2-Amino-2-methyl-1-propanol (AMP), a sterically hindered amine, exhibits a much higher CO2 absorption rate relative to tertiary amine diethylethanolamine (DEEA), while both yield bicarbonate as a major product in aqueous solution, despite their similar basicity. We present molecular mechanisms underlying the significant difference of CO2 absorption rate based on ab initio molecular dynamics simulations combined with metadynamics. Our calculations predict the free energy barrier for base-catalyzed CO2 hydration to be lower in aqueous AMP compared to DEEA...
November 28, 2017: Physical Chemistry Chemical Physics: PCCP
Hui-Min Qin, Zhangliang Zhu, Zheng Ma, Panpan Xu, Qianqian Guo, Songtao Li, Jian-Wen Wang, Shuhong Mao, Fufeng Liu, Fuping Lu
Cholesterol oxidase catalyzes the oxidation and isomerization of the cholestane substrates leading to the addition of a hydroxyl group at the C3 position. Rational engineering of the cholesterol oxidase from Pimelobacter simplex (PsChO) was performed. Mutagenesis of V64 and F70 improved the catalytic activities toward cholestane substrates. Molecular dynamics simulations, together with structure-activity relationship analysis, revealed that both V64C and F70V increased the binding free energy between PsChO mutants and cholesterol...
November 27, 2017: Scientific Reports
Majda Misini Ignjatović, Paulius Mikulskis, Pär Söderhjelm, Ulf Ryde
We have studied whether calculations of the binding free energy of small ligands to a protein by the MM/GBSA approach (molecular mechanics combined with generalized Born and surface area solvation) can be sped up by including only a restricted number of atoms close to the ligand. If the protein is truncated before the molecular dynamics (MD) simulations, quite large changes are observed for the calculated binding energies, for example, 4 kJ/mol average difference for a radius of 19 Å for the binding of nine phenol derivatives to ferritin...
November 26, 2017: Journal of Computational Chemistry
Shuang-Fei Zhu, Shu-Hai Zhang, Rui-Jun Gou, Gang Han, Chun-Lei Wu, Fu-de Ren
The effects of the molar ratio, temperature, and solvent on the formation of the cocrystal explosive DNP/CL-20 were investigated using molecular dynamics (MD) simulation. The cocrystal structure was predicted through Monte Carlo (MC) simulation and using first-principles methods. The results showed that the DNP/CL-20 cocrystal might be more stable in the molar ratio 1:1 near to 318 K, and the most probable cocrystal crystallizes in the triclinic crystal system with the space group P[Formula: see text]. Cocrystallization was more likely to occur in methanol and ethanol at 308 K as a result of solvent effects...
November 24, 2017: Journal of Molecular Modeling
Pierpaolo Cacciotto, Venkata K Ramaswamy, Giuliano Malloci, Paolo Ruggerone, Attilio V Vargiu
Efflux pumps of the resistance nodulation division (RND) superfamily are among the major contributors to intrinsic and acquired multidrug resistance in Gram-negative bacteria. Structural information on AcrAB-TolC and MexAB-OprM, major efflux pumps of Escherichia coli and Pseudomonas aeruginosa respectively, boosted intensive research aimed at understanding the molecular mechanisms ruling the active extrusion processes. In particular, several studies were devoted to the understanding of the determinants behind the extraordinary broad specificity of the RND transporters AcrB and MexB...
2018: Methods in Molecular Biology
Jing Xu, Barbara J Finlayson-Pitts, R Benny Gerber
Mechanisms of particle formation and growth in the atmosphere are of great interest due to their impacts on climate, health and visibility. However, the microscopic structures and related properties of the smallest nanoparticles are not known. In this paper we pursue computationally a microscopic description for the formation and growth of methanesulfonic acid (MSA) and methylamine (MA) particles under dry conditions. Energetic and dynamics simulations were used to assess the stabilities of proposed model structures for these particles...
November 27, 2017: Physical Chemistry Chemical Physics: PCCP
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"