Figure - uploaded by Levi C T Pierce
Content may be subject to copyright.
![Construction of the desired modified potential: The estimated variation of the potential energy of FAD as a function of the reaction coordinate ρ 1 obtained from the standard AMD (cf. Fig. 4) is shown by the dashed black line. A series of points (blue squares) describing the desired modified potential were defined manually and fit to a simple polynomial function [red line, Eq. (10)]. The desired modified potential lies above the true potential across the entire reaction space of interest, –2.8 Å < ρ 1 < 2.8 Å.](profile/Levi-Pierce-2/publication/51104133/figure/fig1/AS:287810113294357@1445630686747/Construction-of-the-desired-modified-potential-The-estimated-variation-of-the-potential.png)
Construction of the desired modified potential: The estimated variation of the potential energy of FAD as a function of the reaction coordinate ρ 1 obtained from the standard AMD (cf. Fig. 4) is shown by the dashed black line. A series of points (blue squares) describing the desired modified potential were defined manually and fit to a simple polynomial function [red line, Eq. (10)]. The desired modified potential lies above the true potential across the entire reaction space of interest, –2.8 Å < ρ 1 < 2.8 Å.
Source publication
A biased potential molecular dynamics simulation approach, accelerated molecular dynamics (AMD), has been implemented in the framework of ab initio molecular dynamics for the study of chemical reactions. Using two examples, the double proton transfer reaction in formic acid dimer and the hypothetical adiabatic ring opening and subsequent rearrangem...
Contexts in source publication
Context 1
... spends a large amount of time exploring high energy, unrealistic regions of the configurational space during the Ad-AMD simulation. Finally, the modified poten- tial should lie below the true potential outside the reaction space of interest. In defined above, a series of points describing the desired modi- fied potential were defined manually (Fig. 5, blue squares): At ρ 1 = 0 Å, the modified PES was fixed 8.5 kcal/mol above the true potential energy of the thermodynamically stable state, V 0 , and therefore, at least 1 kcal/mol above the estimated true PES at the transition state. The modified potential energy min- ima were placed at ρ 1 = +/-1.4 Å, which coincides exactly with ...Context 2
... potential was 0.5 kcal/mol. Two further points were defined at ρ 1 = +/-2.8 Å that intercept the underlying PES. A few interstitial points were then manually added, maintaining the symmetric properties of the modified PES and these points were fitted to a simple polynomial function. The resulting de- sired modified potential (shown in red in Fig. 5) is given ...Similar publications
The photocatalyzed oxidative decompositions of solid particles of polyvinylchloride (PVC; size about 100 to 200 μm), of the polyvinylidene chloride copolymer (95% PVC/5% PVLC; size ∼ 400–600 μm), and a PVC film have been examined in suspensions of titania and zinc oxide illuminated by UV light and/or by natural sunlight. Dechlorination and evolutio...
The aim of the study was to determine the anti-pathogenic activity on the body-surface of bee workers after
applying selected acaricides, such as Amitraz or oxalic and formic acids. In two consecutive years, four
experimental groups (5 colonies per group) were created. The 1st group was the control, the 2nd was treated
with Apiwarol, the 3rd with o...
p>An experiment was conducted to determine the effect of organic acids (acetic, butyric, citric and formic acids) on growth and nutrient digestibility of broilers. One hundred fifty (150) day old Hubbard chicks were used. There were five dietary treatments such viz Diet 1 as control contained no organic acid, diets 2, 3, 4, and 5 contained 0.25% ac...
The most important concern of sandstone matrix acidizing is to increase the formation permeability by removing the silica particles. To accomplish this, the mud acid (HF: HCl) has been utilized successfully for many years to stimulate the sandstone formations, but still it has many complexities. This paper presents the results of laboratory investi...
Organic acids are spontaneously generated in significant concentrations during natural ageing of all cellulose-based papers, the alkaline ones included. The present study reviews the paper degradation research devoted to the identification and determination of the role of light products formed during paper ageing. Accelerated ageing was performed a...
Citations
... An accurate determination of the potential energy of a molecular system as a function of the atomic positions is the path to unlocking the access and understanding of a multitude of physicochemical observables such as vibrational spectra and chemical reaction rates 3,4 . A conventionally adopted strategy to explore the PES of molecules or molecular assemblies in an unbiased way beyond the equilibrium region is performing ab initio molecular dynamics simulations (AIMD) 5,6 . However, given the intrinsic high-dimensionality of the PESs (3N at −6 dimensions for a molecule with N at atoms), the exploration of the vast configurational space in chemical processes-involving isomerization, bond-breaking, or proton transfer-requires a broad sampling of the phase space, long timescale simulations, or both, thereby posing a considerable challenge to computational chemistry research. ...
Multidimensional surfaces of quantum chemical properties, such as potential energies and dipole moments, are common targets for machine learning, requiring the development of robust and diverse databases extensively exploring molecular configurational spaces. Here we composed the WS22 database covering several quantum mechanical (QM) properties (including potential energies, forces, dipole moments, polarizabilities, HOMO, and LUMO energies) for ten flexible organic molecules of increasing complexity and with up to 22 atoms. This database consists of 1.18 million equilibrium and non-equilibrium geometries carefully sampled from Wigner distributions centered at different equilibrium conformations (either at the ground or excited electronic states) and further augmented with interpolated structures. The diversity of our datasets is demonstrated by visualizing the geometries distribution with dimensionality reduction as well as via comparison of statistical features of the QM properties with those available in existing datasets. Our sampling targets broader quantum mechanical distribution of the configurational space than provided by commonly used sampling through classical molecular dynamics, upping the challenge for machine learning models.
... 19,20 Excited state properties can be studied by means of excited-state ab-initio dynamics, 21-24 with non adiabatic schemes [25][26][27][28][29] or surface-hopping based techniques, [30][31][32][33][34] focusing a particular attention in reaching sampling acceleration in excited states. [35][36][37] Although these methods are highly accurate, for large systems they still require a substantial amount of CPU time and memory, which ultimately limit their predictive power to only selected portions of the molecules. ...
The π-rich rings of conjugated polymers and molecular rotors shape their typical properties, allowing a variety of chemical and photoresponsive phenomena. Herein, we present a computational method in the framework of classical simulations to estimate the free-energy gap between ground and excited states of oligofluorenes, a class of molecular rotors widely used in optoelectronic devices due to the inner torsional rotation triggered by light irradiation. We devised multiple sets of free-energy simulations in combination with free-energy perturbation theory to predict the free-energy gap between the ground and the first excited state. The computed excitation energies show good agreement with experiments. The approach herein presented allows to achieve at the same time comprehensive sampling of the conformational landscape and accurate estimates of the excited state free-energy landscapes.
... To analyze possible origins of the metal adatoms observed in our and in previouse xperiments on Ullmann couplings on surfaces, we carried out accelerated ab initio molecular dynamics simulations [17,18] of the dehalogenation reactiono nC u(111). Figure 4s hows the crucial steps of the extraction process occurring during the AIMD simulation. ...
... The bottom layer of the slab was kept fixed. Accelerated AIMD simulations [17,18] were carried out using an inhouse modification of the package CPMD. [22] The modified potential is given by Equation (1) ...
Possible origins of the formation of organometallic intermediates in on-surface Ullmann couplings have been investigated by surface tunneling microscopy (STM) and density functional theory (DFT) calculations. We consider the case of iodobenzenes on the coinage metals Au, Ag and Cu. We found experimental evidence for the formation of surface vacancies and the presence of metal adatoms in these coupling reactions, which are taken as a hint for the reactive extraction of surface atoms by adsorbates. In a second step, we demonstrate by ab initio molecular dynamics calculations for aryl-iodides on copper that metal atoms can be pulled out of the surface to form metalorganic species. By contrast, a thermally activated provision of a metal atom from the surface to form an adatom is energetically unfavourable. Finally, we investigate the mechanism and energetics of the reactive extraction of surface metal atoms by means of (climbing-image) nudged-elastic-band density-functional theory calculations for iodobenzene on copper, silver and gold, and analyze our results in the light of the experimental findings.
... Unlike the above-mentioned biasing simulation methods, aMD does not require pre-defined reaction coordinate(s), which can be advantageous for exploring the biomolecular conformational space without a priori knowledge or restraints. aMD has been successfully applied to a number of biological systems 26,27,28,29,30 and hundreds-of-nanoseconds aMD simulations have been shown to capture millisecond-timescale events in both globular and membrane proteins 31,32,33 . ...
A novel Gaussian Accelerated Molecular Dynamics (GaMD) method has been developed for simultaneous unconstrained enhanced sampling and free energy calculation of biomolecules. Without the need to set predefined reaction coordinates, GaMD enables unconstrained enhanced sampling of the biomolecules. Furthermore, by constructing a boost potential that follows a Gaussian distribution, accurate reweighting of GaMD simulations is achieved via cumulant expansion to the second order. The free energy profiles obtained from GaMD simulations allow us to identify distinct low energy states of the biomolecules and characterize biomolecular structural dynamics quantitatively. In this chapter, we present the theory of GaMD, its implementation in the widely used molecular dynamics software packages (AMBER and NAMD), and applications to the alanine dipeptide biomolecular model system, protein folding, biomolecular large-scale conformational transitions, and biomolecular recognition.
... In addition, a number of different forms of aMD have been developed to improve the sampling statistics of bimolecular configurations, including the windowed aMD designed to protect the high-energy barriers [88], adaptive aMD [89], rotatable aMD or RaMD [90] and selective aMD [91]. With the enhanced sampling power, aMD has also been combined with many other techniques, including the thermodynamic integration [92], replica exchange [93][94][95], constant pH MD [96] and ab initio MD [97,98], for various classical and quantum computational simulations of biomolecules. ...
Free energy calculations are central to understanding the structure, dynamics and function of biomolecules. Yet insufficient sampling of biomolecular configurations is often regarded as one of the main sources of error. Many enhanced sampling techniques have been developed to address this issue. Notably, enhanced sampling methods based on biasing collective variables (CVs), including the widely used umbrella sampling, adaptive biasing force and metadynamics, have been discussed in a recent excellent review (Abrams and Bussi, Entropy, 2014). Here, we aim to review enhanced sampling methods that do not require predefined system-dependent CVs for biomolecular simulations and as such do not suffer from the hidden energy barrier problem as encountered in the CV-biasing methods. These methods include, but are not limited to, replica exchange/parallel tempering, self-guided molecular/Langevin dynamics, essential energy space random walk and accelerated molecular dynamics. While it is overwhelming to describe all details of each method, we provide a summary of the methods along with the applications and offer our perspectives. We conclude with challenges and prospects of the unconstrained enhanced sampling methods for accurate biomolecular free energy calculations.
Gaussian accelerated molecular dynamics (GaMD) is recognized as a popular enhanced sampling method for tackling long-standing challenges in biomolecular simulations. Inspired by GaMD, Sigmoid accelerated molecular dynamics (SaMD) is proposed in this work by adding a Sigmoid boost potential to improve the balance between the highest acceleration and accurate reweighting. Compared with GaMD, SaMD extends the accessible time scale and improves the computational efficiency as tested in three tasks. In the alanine dipeptide task, SaMD can produce the free energy landscape with better accuracy and efficiency. In the chignolin folding task, the estimated Gibbs free energy difference can converge to the experimental value ∼30% faster. In the protein-ligand binding task, the bound conformations are closer to the crystal structure with a minimal ligand root-mean-square deviation of 1.7 Å. The binding of the ligand XK263 to the HIV protease is reproduced by SaMD in ∼60% less simulation time.
Shristi Pawnikar, Apurba Bhattarai, Jinan Wang, Yinglong Miao Center for Computational Biology and Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66047, USACorrespondence: Yinglong MiaoCenter for Computational Biology, University of Kansas, 2030 Becker Drive, Room 200D MRB, Lawrence, KS, 66047, USAEmail miao@ku.eduAbstract: Biomolecular recognition such as binding of small molecules, nucleic acids, peptides and proteins to their target receptors plays key roles in cellular function and has been targeted for therapeutic drug design. Molecular dynamics (MD) is a computational approach to analyze these binding processes at an atomistic level, which provides valuable understandings of the mechanisms of biomolecular recognition. However, the rather slow biomolecular binding events often present challenges for conventional MD (cMD), due to limited simulation timescales (typically over hundreds of nanoseconds to tens of microseconds). In this regard, enhanced sampling methods, particularly accelerated MD (aMD), have proven useful to bridge the gap and enable all-atom simulations of biomolecular binding events. Here, we will review the recent method developments of Gaussian aMD (GaMD), ligand GaMD (LiGaMD) and peptide GaMD (Pep-GaMD), which have greatly expanded our capabilities to simulate biomolecular binding processes. Spontaneous binding of various biomolecules to their receptors has been successfully simulated by GaMD. Microsecond LiGaMD and Pep-GaMD simulations have captured repetitive binding and dissociation of small-molecule ligands and highly flexible peptides, and thus enabled ligand/peptide binding thermodynamics and kinetics calculations. We will also present relevant application studies in simulations of important drug targets and future perspectives for rational computer-aided drug design.Keywords: biomolecular recognition, accelerated molecular dynamics, thermodynamics, kinetics, drug design
Molecular dynamics (MD) is a powerful tool to investigate microscopic transport of atoms and molecules in condensed matter. However, there lies a large class of systems wherein atomic diffusion is too slow a process relative to the feasible time scales of typical atomistic simulations. Here, we demonstrate that with judicial implementation of a metadynamics (MTD) technique, the microscopic mechanism of atomic transport in solids can be accessed within a reasonable computational time. The calculations are carried out on the two end members of the true NASICON solid solutions, namely NaZr2(PO4)3 and Na4Zr2(SiO4)3, wherein Na+ diffusion is too slow to be accessed through standard MD simulations. The study also provides fresh insights on correlated ion hops and their implications on the effective diffusion barrier. The results are compared with climbing image nudged elastic band (CI-NEB) calculation, and available experimental results.
The light-induced surface modification of a thin film of poly-(disperse orange-3-methylmethacrylate) is investigated computationally using atomistic molecular dynamics simulations specifically tailored to include photoisomerization dynamics. For a model surface consisting of a periodic pattern of alternating irradiated and dark spots, it is shown that repeated photoisomerization in the irradiated areas initially leads to a local temperature increase and a raised surface profile accompanied by a migration of molecules away from the bright spots. After switching off the light source and letting the system cool down, this leads to an inversion of the surface profile, i.e., dips in the bright spots and bumps in the dark spots. To separate the effect of photoisomerization from the pure heating effect, a second simulation is performed in which no photoisomerization is allowed to occur in the bright spots, but the equivalent amount of energy is introduced there locally in the form of heat. This also leads to a raised surface in these areas; however, no outward migration of molecules is observed and the surface pattern practically vanishes when the system is subsequently cooled back to room temperature.
We present the isolated gas phase infrared spectra of formic acid dimer, (HCOOH)2, and its deuterated counterpart formic-d acid, (DCOOH)2, at room temperature. The formic acid dimer spectrum was obtained by spectral subtraction of a spectrum of formic acid vapor recorded at low pressure from that recorded at a higher pressure. The spectra of formic acid vapor contain features from both formic acid monomer and formic acid dimer, but at low and high pressures of formic acid, the equilibrium is pushed towards the monomer and dimer, respectively. A similar approach was used for the formic-d acid dimer. Building on the previous development of the Molecular Mechanics with Proton Transfer (MMPT) force field for simulating proton transfer reactions, molecular dynamics (MD) simulations were carried out to interpret the experimental spectra in the OH-stretching region. Within the framework of MMPT, a combination of symmetric single and double minimum potential energy surfaces (PESs) provides a good description of the double proton transfer PES. In a next step, potential morphing together with electronic structure calculations at the B3LYP and MP2 level of theory was used to align the computed and experimentally observed spectral features in the OH-stretching region. From this analysis, a barrier for double proton transfer between 5 and 7 kcal mol(-1) was derived, which compares with a CCSD(T)/aug-cc-pVTZ calculated barrier of 7.9 kcal mol(-1). Such a combination of experimental and computational techniques for estimating barriers for proton transfer in gas phase systems is generic and holds promise for further improved PESs and energetics of these important systems. Additional MD simulations at the semi-empirical DFTB level of theory agree quite well for the center band position but underestimate the width of the OH-stretching band.
