We present molecular dynamics (MD) trajectories of water solutions of eight zwitterionic amino-acids (L- form) glycine (GLY), alanine (ALA), proline (PRO), threonine (THR), leucine (LEU), glutamine (GLN), histidine (HIS) and tyrosine (TYR) using various force field (OPLS-AA, Amber99ff-SB, GROMOS96 54a7, CHARMM19) and water model (SPC/E, TIP3P) combinations. Additionally, we present OPLS-AA molecular dynamics (MD) trajectories for alanine (ALA), leucine (LEU), glutamine (GLN), and tyrosine (TYR) varying the values of major force field parameters: charge on all amino acid atoms, bond length (all amino acid bonds), Lennard-Jones potential epsilon parameter and stiffness of bond angles. Our data enable to uncover sensitivity of molecular dynamics derived analysis to variation of force field and water models and force field parameters. This data set was used to understand the effect of molecular dynamics parameters on dielectric properties of amino acid solutions [1].

• Klíčová slova
• Amino acid, Biomolecules, Dielectric spectroscopy, Force field, Molecular dynamics,
• Publikační typ
• časopisecké články MeSH

Macromolecular crowding has profound effects on the mobility of proteins, with strong implications on the rates of intracellular processes. To describe the dynamics of crowded environments, detailed molecular models are needed, capturing the structures and interactions arising in the crowded system. In this work, we present OPEPv7, which is a coarse-grained force field at amino-acid resolution, suited for rigid-body simulations of the structure and dynamics of crowded solutions formed by globular proteins. Using the OPEP protein model as a starting point, we have refined the intermolecular interactions to match the experimentally observed dynamical slowdown caused by crowding. The resulting force field successfully reproduces the diffusion slowdown in homogeneous and heterogeneous protein solutions at different crowding conditions. Coupled with the lattice Boltzmann technique, it allows the study of dynamical phenomena in protein assemblies and opens the way for the in silico rheology of protein solutions.

• MeSH
• počítačová simulace MeSH
• proteiny * chemie   MeSH
• roztoky MeSH
• simulace molekulární dynamiky * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteiny * MeSH
• roztoky MeSH

Electrostatic interactions have a determining role in the conformational and dynamic behavior of polyelectrolyte molecules. In this study, anionic polyelectrolyte molecules, poly(glutamic acid) (PGA) and poly(aspartic acid) (PASA), in a water solution with the most commonly used K+ or Na+ counterions, were investigated using atomistic molecular dynamics (MD) simulations. We performed a comparison of seven popular force fields, namely AMBER99SB-ILDN, AMBER14SB, AMBER-FB15, CHARMM22*, CHARMM27, CHARMM36m and OPLS-AA/L, both with their native parameters and using two common corrections for overbinding of ions, the non-bonded fix (NBFIX), and electronic continuum corrections (ECC). These corrections were originally introduced to correct for the often-reported problem concerning the overbinding of ions to the charged groups of polyelectrolytes. In this work, a comparison of the simulation results with existing experimental data revealed several differences between the investigated force fields. The data from these simulations and comparisons with previous experimental data were then used to determine the limitations and strengths of these force fields in the context of the structural and dynamic properties of anionic polyamino acids. Physical properties, such as molecular sizes, local structure, and dynamics, were studied using two types of common counterions, namely potassium and sodium. The results show that, in some cases, both the macroion size and dynamics depend strongly on the models (parameters) for the counterions due to strong overbinding of the ions and charged side chain groups. The local structures and dynamics are more sensitive to dihedral angle parameterization, resulting in a preference for defined monomer conformations and the type of correction used. We also provide recommendations based on the results.

• Klíčová slova
• carboxyls, counterions, force fields, ions, molecular dynamics, peptides and proteins,
• Publikační typ
• časopisecké články MeSH

The calculation of caloric properties such as heat capacity, Joule-Thomson coefficients, and the speed of sound by classical force-field-based molecular simulation methodology has received scant attention in the literature, particularly for systems composed of complex molecules whose force fields (FFs) are characterized by a combination of intramolecular and intermolecular terms. The calculation of a thermodynamic property for a system whose molecules are described by such a FF involves the calculation of the residual property prior to its addition to the corresponding ideal-gas property, the latter of which is separately calculated, either using thermochemical compilations or nowadays accurate quantum mechanical calculations. Although the simulation of a volumetric residual property proceeds by simply replacing the intermolecular FF in the rigid molecule case by the total (intramolecular plus intermolecular) FF, this is not the case for a caloric property. We describe the correct methodology required to perform such calculations and illustrate it in this paper for the case of the internal energy and the enthalpy and their corresponding molar heat capacities. We provide numerical results for cP, one of the most important caloric properties. We also consider approximations to the correct calculation procedure previously used in the literature and illustrate their consequences for the examples of the relatively simple molecule 2-propanol, CH3CH(OH)CH3, and for the more complex molecule monoethanolamine, HO(CH2)2NH2, an important fluid used in carbon capture.

• Publikační typ
• časopisecké články MeSH

Phosphorylation of serine, threonine, and tyrosine is one of the most frequently occurring and crucial post-translational modifications of proteins often associated with important structural and functional changes. We investigated the direct effect of phosphorylation on the intrinsic conformational preferences of amino acids as a potential trigger of larger structural events. We conducted a comparative study of force fields on terminally capped amino acids (dipeptides) as the simplest model for phosphorylation. Our bias-exchange metadynamics simulations revealed that all model dipeptides sampled a great heterogeneity of ensembles affected by introduction of mono- and dianionic phosphate groups. However, the detected changes in populations of backbone conformers and side-chain rotamers did not reveal a strong discriminatory shift in preferences, as could be anticipated for the bulky, charged phosphate group. Furthermore, the AMBER and CHARMM force fields provided inconsistent populations of individual conformers as well as net structural trends upon phosphorylation. Detailed analysis of ensembles revealed competition between hydration and formation of internal hydrogen bonds involving amide hydrogens and the phosphate group. The observed difference in hydration free energy and potential for hydrogen bonding in individual force fields could be attributed to the different partial atomic charges used in each force field and, hence, the different parametrization strategies. Nevertheless, conformational propensities and net structural changes upon phosphorylation are difficult to extract from experimental measurements, and existing experimental data provide limited guidance for force field assessment and further development.

• MeSH
• fosforylace MeSH
• konformace proteinů MeSH
• serin metabolismus   MeSH
• simulace molekulární dynamiky MeSH
• threonin metabolismus   MeSH
• tyrosin metabolismus   MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• serin MeSH
• threonin MeSH
• tyrosin MeSH

Accurate simulations of vibrational molecular spectra require precise molecular force fields, at least with cubic and quartic anharmonic corrections beyond the harmonic limits. Generation of such force field terms becomes computationally prohibitive for larger molecules. In this work, an alternate possibility is explored, where approximate anharmonic force field components are obtained from molecular fragments. Transferability properties of the cubic and incomplete quartic fields are discussed and tested on model oligoproline molecules. Automatic transfer schemes including cubic, two and three atomic quartic force constants are developed and implemented. The results indicate that the main vibrational interactions in molecules are local and the anharmonic constants are mostly well amendable to the transfer. Exact anharmonic normal mode force fields of larger molecules compared very well to those obtained from smaller molecular parts. The most important changes in vibrational spectra caused by the anharmonic interactions could be reproduced with two and three atomic force field terms. The transfer scheme thus provides molecular anharmonic force fields without a significant loss of accuracy and brings significant savings of computer time and memory needed to generate molecular vibrational energies and spectra.

• Publikační typ
• časopisecké články MeSH

Cholesterol is a central building block in biomembranes, where it induces orientational order, slows diffusion, renders the membrane stiffer, and drives domain formation. Molecular dynamics (MD) simulations have played a crucial role in resolving these effects at the molecular level; yet, it has recently become evident that different MD force fields predict quantitatively different behavior. Although easily neglected, identifying such limitations is increasingly important as the field rapidly progresses toward simulations of complex membranes mimicking the in vivo conditions: pertinent multicomponent simulations must capture accurately the interactions between their fundamental building blocks, such as phospholipids and cholesterol. Here, we define quantitative quality measures for simulations of binary lipid mixtures in membranes against the C-H bond order parameters and lateral diffusion coefficients from NMR spectroscopy as well as the form factors from X-ray scattering. Based on these measures, we perform a systematic evaluation of the ability of commonly used force fields to describe the structure and dynamics of binary mixtures of palmitoyloleoylphosphatidylcholine (POPC) and cholesterol. None of the tested force fields clearly outperforms the others across the tested properties and conditions. Still, the Slipids parameters provide the best overall performance in our tests, especially when dynamic properties are included in the evaluation. The quality evaluation metrics introduced in this work will, particularly, foster future force field development and refinement for multicomponent membranes using automated approaches.

• MeSH
• cholesterol chemie   MeSH
• fosfatidylcholiny * chemie   MeSH
• lipidové dvojvrstvy * chemie   MeSH
• simulace molekulární dynamiky MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1-palmitoyl-2-oleoylphosphatidylcholine MeSH Prohlížeč
• cholesterol MeSH
• fosfatidylcholiny * MeSH
• lipidové dvojvrstvy * MeSH

Modelling of carbohydrate conformations is a challenging task for force field developers. Three carbohydrate force fields, namely GLYCAM06, GROMOS 45a4 and OPLS were evaluated. Free energies of different ring conformations of beta-D-glucopyranose were calculated using metadynamics in vacuum as well as in explicitly modelled water. All three force fields model the (4)C(1) conformation as the most stable by at least 6kJ/mol, as compared to other conformations. Interconversion from the (4)C(1) to any other conformation is associated with a barrier of no lower than 26kJ/mol. The free energy surface calculated in the GLYCAM06 force field is in remarkably good agreement with the recent Car-Parrinello metadynamics study. The effect of a water environment is relatively low and analogous in all tested force fields. Namely, the presence of water stabilizes the upper-left ((3,O)B) versus bottom-right (B(3,O)) area of Stoddard's plot, relative to the situation in vacuum. Comparison of free and potential surfaces is also provided for vacuum calculations.

• MeSH
• glukosidy chemie   MeSH
• konformace sacharidů MeSH
• simulace molekulární dynamiky * MeSH
• termodynamika MeSH
• voda chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glukosidy MeSH
• voda MeSH

The great physiological relevance of glycolipids is being increasingly recognized, and glycolipid interactions have been shown to be central to cell-cell recognition, neuronal plasticity, protein-ligand recognition, and other important processes. However, detailed molecular-level understanding of these processes remains to be fully resolved. Molecular dynamics simulations could reveal the details of the glycolipid interactions, but the results may be influenced by the choice of the employed force field. Here, we have compared the behavior and properties of GM1, a common, biologically important glycolipid, using the CHARMM36, OPLS, GROMOS, and Amber99-GLYCAM06 (in bilayers comprising SLIPIDS and LIPID14 lipids) force fields in bilayers comprising 1,2-dioleoyl-sn-glycero-3-phosphocholine lipids and compared the results to atomic force microscopy and fluorescence resonance energy transfer experiments. We found discrepancies within the GM1 behavior displayed between the investigated force fields. Based on a direct comparison with complementary experimental results derived from fluorescence and AFM measurements, we recommend using the Amber99-GLYCAM force field in bilayers comprising LIPID14 or SLIPIDS lipids followed by CHARMM36 and OPLS force fields in simulations. The GROMOS force field is not recommended for reproducing the properties of the GM1 head group.

• MeSH
• fosfatidylcholiny chemie   MeSH
• G(M1) gangliosid chemie   MeSH
• kvantová teorie * MeSH
• lipidové dvojvrstvy chemie   MeSH
• mikroskopie atomárních sil MeSH
• molekulární konformace MeSH
• rezonanční přenos fluorescenční energie * MeSH
• simulace molekulární dynamiky MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 1,2-oleoylphosphatidylcholine MeSH Prohlížeč
• fosfatidylcholiny MeSH
• G(M1) gangliosid MeSH
• lipidové dvojvrstvy MeSH

Studies of drug-membrane interactions witness an ever-growing interest, as penetration, accumulation, and positioning of drugs play a crucial role in drug delivery and metabolism in human body. Molecular dynamics simulations complement nicely experimental measurements and provide us with new insight into drug-membrane interactions; however, the quality of the theoretical data dramatically depends on the quality of the force field used. We calculated the free energy profiles of 11 molecules through a model dimyristoylphosphatidylcholine (DMPC) membrane bilayer using five force fields, namely Berger, Slipids, CHARMM36, GAFFlipids, and GROMOS 43A1-S3. For the sake of comparison, we also employed the semicontinuous tool COSMOmic. High correlation was observed between theoretical and experimental partition coefficients (log K). Partition coefficients calculated by all-atomic force fields (Slipids, CHARMM36, and GAFFlipids) and COSMOmic differed by less than 0.75 log units from the experiment and Slipids emerged as the best performing force field. This work provides the following recommendations (i) for a global, systematic and high throughput thermodynamic evaluations (e.g., log K) of drugs COSMOmic is a tool of choice due to low computational costs; (ii) for studies of the hydrophilic molecules CHARMM36 should be considered; and (iii) for studies of more complex systems, taking into account all pros and cons, Slipids is the force field of choice.

• Publikační typ
• časopisecké články MeSH