Molecular dynamics simulation protocol

The SHAKE (46) procedure for constraining all hydrogen atoms, 2 fsec time step and the 9 A cutoff has been applied in all simulations. Calculations have been performed at the temperature of 300K. Results have been analyzed based on the trajectories saved after each 1 psec of simulations. The technical details concerning molecular dynamics simulations protocol and the results are described in Cieplak et al. 47). 

How can we apply molecular dynamics simulations practically. This section gives a brief outline of a typical MD scenario. Imagine that you are interested in the response of a protein to changes in the amino add sequence, i.e., to point mutations. In this case, it is appropriate to divide the analysis into a static and a dynamic part. What we need first is a reference system, because it is advisable to base the interpretation of the calculated data on changes compared with other simulations. By taking this relative point of view, one hopes that possible errors introduced due to the assumptions and simplifications within the potential energy function may cancel out. All kinds of simulations, analyses, etc., should always be carried out for the reference and the model systems, applying the same simulation protocols. 

Molecular dynamics simulations are el ficient for searching the conformational space of medium-sized molecules and peptides. Different protocols can increase the elTicieiicy of the search and reduce the computer time needed to sample adequately the available conformations. 

Every molecular dynamics simulation consists of several steps. Put together, these steps are called a simulation protocol. The main steps common to most dynamic simulation protocols are the following. 

We have presented a simple protocol to run MD simulations for systems of interest. There are, however, some tricks to improve the efficiency and accuracy of molecular dynamics simulations. Some of these techniques, which are discussed later in the book, are today considered standard practice. These methods address diverse issues ranging from efficient force field evaluation to simplified solvent representations. 

A comprehensive test of computational protocols applied for the short time dynamics of the photolysed Mb-CO complex is presented by Meller and Elber [110]. 270 different 10 ps molecular dynamics simulations were carried out using two different solvation boxes, two differenc types of electrostatic cutoffs and two different treatments of the photodissociated ligand. In addition, both the wild-type and the Leu29Phe mutant were treated. 9 different setups were combined from the variables described and 30 trajectories were generated for all. Results presented are averages over these 30 trajectories. Calculations were performed using a combination of the AMBER [111] and OPES [112] force fields, the heme model of Kuczera et al. [16] and approximately 2700 TIP3P... 

In order to test the hypothesis that efficient promoter sequences will be more likely to acquire an A-DNA like conformation than other sequences, we carried out a collection of molecular dynamics simulations of the DNA double stranded dodecamers listed in Table 3. All these simulations were done with the CHARMM23 potential [93], in the presence of explicit solvent (-3500 TIP3 [99] water molecules) and 22 sodium ions (the simulation protocol is detailed in [89,100,101]). The DNA sequences were chosen to include known functional promoters (MLP, MLP2, AT, E4, 6T, CYCl, EFIA, and R28), nonfunctional promoters which could function with a mutant TBP (2C and 7G) [69,70], an inosine variant which can promote transcription (I) [102], and negative controls (GC, POLYA). This collection of sequences also includes two pairs of TATA boxes located in different contexts (MLP and MLP2, and AT and E4) in order to explore the sensitivity of the results to end effects. All the simulations started from a canonical B-DNA conformation and relaxed into a structure closer to A-DNA after 2 ns of simulation, not all the sequences achieved the same structure, as shown in Table 3, an indication that the simulation protocol is capable of identifying sequence dependent features. 

We investigated freezing of water and salt solutions by means of molecular dynamics simulations. We first established a robust simulation protocol for water freezing and than applied this approach to the study of the brine rejection process. Brine rejection was observed for a series of systems with varying salt concentration. We showed the anti-freeze... 

Not all molecular properties are, however, of local nature, which lend themselves to efficient computational schemes. Molecular vibrations are typically non-local and delocalized. Nevertheless, it is possible even in such cases to design a tailored quantum chemical method, the Mode-Tracking protocol [164], for the selective calculation of only those vibrations relevant for a certain scientific context. For the selective calculation of various types of vibrational spectra we refer the interested reader to the reviews in Refs. [165, 166]. It should be mentioned that molecular dynamics simulations offer different routes to spectra through autocorrelation functions. 

Genheden S, Ryde U (2011) A comparison of different initialization protocols to obtain statistically independent molecular dynamics simulations. J Comput Chem 32 187-195... 

Several molecular dynamics simulation approaches are available, including regular simulation, constrained simulation, and simulated annealing techniques. In addition, the simulated annealing dynamics simulation also was popular in computational chemistry studies of proteins and drug molecules (34.44.45). A common experimental protocol has been widely used in molecular dynamics simulation as following (34.46.47) ... 

Chen J, Brooks CLI, Wright PE (2004) Model-free analysis of protein dynamics assessment of accuracy and model selection protocols based on molecular dynamics simulation. J Biomol NMR 29 243-257... 

This conclusion raises an additional question. In our classical molecular dynamics simulations, the excess kinetic energy was uniformly added to all heme atoms. Does the observed simulated heme cooling rate depend upon the mode of excitation No dependence on the mode of excitation was observed in the classical simulations. In addition to the V4 and V7 modes, other modes, including iron out-of-plane motions, are initially excited, leading to a broad excitation of heme atoms in the initially excited state. It is reasonable to assume that, ignoring coherence, that state of excitation is similar to our uniform heating protocol. 

Molecular dynamics simulations of DNA duplexes go back nearly 15 years and useful insights into the structure, dynamics and hydration of nucleic acids has emerged from these studies. Nonetheless, the increase in computer power, dlowing one to simulate into the nanosecond time range, with die inclusion of explicit solvent and coimterions and improvements in the simulation protocols (force fields and efficient ways to include long range electrostatic effects) has made the last few years particularly fruitfiil. 

FIGURE 7.10 Side view models showing the system and protocol adopted for the reactive molecular dynamics simulation of the interaction of chloride ions with passivated copper surfaces. Left Cu(l 11) slab covered by CU2O thin films with O-deficient (top) and O-enriched (bottom) terminations after thermal relaxation at 300 K. Middle filling the gap with 20 M Cl" aqueous solution (pH 7). Right complete system after relaxation for 250 ps at 300 K showing preferential interaction of the chlorides ions with the O-deficient surface. Periodic boundary conditions apply along the x-, y-, and z-directions.Adapted from Jeon et al. [135], 1229, with permission from the Ameriean Chemical Society. 

Webber, J.B.W., Anderson, R., Strange, J.H., and Tohidi, B., 2007a. Clathrate formation and dissociation in vapour/water/ice/hydrate systems in SBA-15, Sol-Gel and CPG porous media, as probed by NMR relaxation, novel protocol NMR cryoporometry, neutron scattering and ab-initio quantum-mechanical molecular dynamics simulation. Magn. Reson. Imag. 25 533-536. 

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