Bridging Water Molecules Research Articles

Proton-Conductive Coordination Polymers Based on Diphenylsulfone-3,3'-disulfo-4,4'-dicarboxylate with Well-Defined Hydrogen Bonding Networks.

The diphenylsulfone-3,3'-disulfo-4,4'-dicarboxylic acid (H4-DPSDSDC) ligand and its coordination polymers, [K2Zn(C14H6S3O12)(H2O)4]n (1) and {[Cu3(μ3-OH)2(C14H6S3O12)(H2O)3(DMF)]·3(H2O)}n (2) (C14H6S3O12 = diphenylsulfone-3,3'-disulfo-4,4'-dicarboxylate), were synthesized. The Zn(H2O)4 units in 1 are connected by DPSDSDC4- ligands to generate a one-dimensional (1D) chain, which is bridged by K-O bonds associated with bridging water molecules and sulfonate groups to yield a two-dimensional (2D) layer. In 2, the 1D hydroxyl-bridging Cu(II) chains are connected by DPSDSDC4- ligands to give a 2D layer. The 2D layers in 1 and 2 are further connected by interlayered hydrogen bonds to give three-dimensional (3D) frameworks. Compounds 1 and 2 have good conductivities of 1.57 × 10-4 and 5.32 × 10-5 S cm-1, respectively. Continuous well-defined hydrogen bonding networks associated with water molecules, sulfonate groups, and carboxylate groups were observed in compounds 1 and 2. Such hydrogen bonding networks provide hydrophilic domains and effective transfer pathways for protons. Here, we present elegant examples of a precise determination of the pathways for proton transport.

Sulfate, Bisulfate, and Hydrogen Co-adsorption on Pt(111) and Au(111) in an Electrochemical Environment.

The co-adsorption of sulfate, bisulfate and hydrogen on Pt(111) and Au(111) electrodes was studied based on periodic density functional calculations with the aqueous electrolyte represented by both explicit and implicit solvent models. The influence of the electrochemical control parameters such as the electrode potential and pH was taken into account in a grand-canonical approach. Thus, phase diagrams of the stable coadsorption phases as a function of the electrochemical potential and Pourbaix diagrams have been derived which well reproduce experimental findings. We demonstrate that it is necessary to include explicit water molecules in order to determine the stable adsorbate phases as the (bi)sulfate adsorbates rows become significantly stabilized by bridging water molecules.

Conformational Motions and Water Networks at the α/β Interface in E. coli Ribonucleotide Reductase.

Ribonucleotide reductases (RNRs) catalyze the conversion of all four ribonucleotides to deoxyribonucleotides and are essential for DNA synthesis in all organisms. The active form of E. coli Ia RNR is composed of two homodimers that form the active α2β2 complex. Catalysis is initiated by long-range radical translocation over a ∼32 Å proton-coupled electron transfer (PCET) pathway involving Y356β and Y731α at the interface. Resolving the PCET pathway at the α/β interface has been a long-standing challenge due to the lack of structural data. Herein, molecular dynamics simulations based on a recently solved cryogenic-electron microscopy structure of an active α2β2 complex are performed to examine the structure and fluctuations of interfacial water, as well as the hydrogen-bonding interactions and conformational motions of interfacial residues along the PCET pathway. Our free energy simulations reveal that Y731 is able to sample both a flipped-out conformation, where it points toward the interface to facilitate interfacial PCET with Y356, and a stacked conformation with Y730 to enable collinear PCET with this residue. Y356 and Y731 exhibit hydrogen-bonding interactions with interfacial water molecules and, in some conformations, share a bridging water molecule, suggesting that the primary proton acceptor for PCET from Y356 and from Y731 is interfacial water. The conformational flexibility of Y731 and the hydrogen-bonding interactions of both Y731 and Y356 with interfacial water and hydrogen-bonded water chains appear critical for effective radical translocation along the PCET pathway. These simulations are consistent with biochemical and spectroscopic data and provide previously unattainable atomic-level insights into the fundamental mechanism of RNR.

Role of polar and apolar moieties in water adsorption by humic acids under arid conditions

In arid soils, humic acids (HAs) are used as amendments to improve water uptake from the atmosphere. This method of harvesting water involves several steps depending on the relative humidity (RH). At low RH, water is adsorbed solely on primary sorption sites such as polar groups. As RH increases, more water is adsorbed on polar groups forming secondary sorption sites, which grow as the RH increases. As a result, the neighboring sorption sites can connect to form water molecule bridges (WaMBs). The WaMBs are responsible for the transport of water in the form of clusters into hydrophobic pores resulting in an increase in water content in organic matter (OM), swelling of OM and formation of phase water. HA being a complex mixture complicates the understanding of the relationship between the proportion of polar groups and properties of water. The understanding of these relationships can guide the design of humic-based amendments applicable in arid systems. To address this issue, seven HAs were characterized by nuclear magnetic resonance followed by the investigation of the properties of water (water content, strength of WaMBs and strength of water binding) on the HAs. Results showed that the content of polar groups positively correlated with the amount of water adsorbed by HA and the stability of WaMBs. It was found that presumably apolar moieties such as aromatics and phenols increased the binding energy of water to HA thereby appearing to be responsible for preventing the desiccation. In addition, between 44 and 76% RH, the WaMB stability positively correlated with O-alkyl and peptides moieties. Therefore, both polar and apolar domains influence water properties depending on RH. We conclude that this synergism is an advantage in systems composed of hydrophobic and hydrophilic molecules held together by weak interactions providing high flexibility to the system under arid conditions.

Metal-Metalloligand Coordination Polymer Embedding Triangular Cobalt-Oxo Clusters: Solvent- and Temperature-Induced Crystal to Crystal Transformations and Associated Magnetism.

Reaction of the metalloligand IrIII(ppy-COOH)3 and the anisotropic paramagnetic CoII ion under solvothermal conditions resulted in a metal-metalloligand coordination polymer, [CoII3(μ3-O)(μ-OH2){IrIII(ppy-COO)2(ppy-COOH)}2(H2O)4]·2DMF·xH2O (I). It consists of trimeric Co3O secondary building units (SBUs) bridged by pairs of Ir to form chains of alternate orthogonal squares. The compound undergoes two single-crystal to single-crystal transformations while retaining its general structural features. A chemical transformation occurs to give [CoII3(μ3-O){IrIII(ppy-COO)2(ppy-COOH)}2(H2O)4(DMF)]·DMF·H2O (II) by soaking in acetone, where a bridging water molecule departs and the solvent DMF bonds to the vacant site of the Co center. Both I and II undergo a temperature-induced transformation to [CoII3(μ3-O){IrIII(ppy-COO)2(ppy-COOH)}2(H2O)3(DMF)]·DMF (III), where one more coordinated water molecule is lost. The major difference in the three phases is in the Co coordination spheres, which have considerable consequences on the magnetism. Compound I displays paramagnetism down to 2 K, whereas II and III show weak ferromagnetism with TC values of 14 and 17 K, respectively.

Rigorous analysis of free solution glycosaminoglycan dynamics using simple, new tools.

Heparin/heparan sulfates (H/HS) are ubiquitous biopolymers that interact with many proteins to induce a range of biological functions. Unfortunately, how these biopolymers recognize their preferred protein targets remain poorly understood. It is suggested that computational simulations offer attractive avenues but a number of challenges, e.g., difficulty of selecting a comprehensive force field, few simple tools to interpret data, among others, remain. This work addresses several such challenges so as to help ease the implementation and analysis of computational experiments. First, this work presents a rigorous comparison of two different recent force fields, CHARMM36 and GLYCAM06, for H/HS studies. Second, it introduces two new straightforward parameters, i.e., end-to-end distance and minimum volume enclosing ellipsoid, to understand the myriad conformational forms of oligosaccharides that evolve over time in water. Third, it presents an application to elucidate the number and nature of inter and intramolecular, nondirect bridging water molecules, which help stabilize unique forms of H/HS. The results show that nonspecialists can use either CHARMM36 or GLYCAM06 force fields because both gave comparable results, albeit with small differences. The comparative study shows that the HS hexasaccharide samples a range of conformations with nearly equivalent energies, which could be the reason for its recognition by different proteins. Finally, analysis of the nondirect water bridges across the dynamics trajectory shows their importance in stabilization of certain conformational forms, which may become important for protein recognition. Overall, the work aids nonspecialists employ computational studies for understanding the solution behavior of H/HS.

N-[(E)-Quinolin-2-yl-methyl-idene]-1,2,4-triazol-4-amine hemihydrate.

The title hemihydrate, C12H9N5·0.5H2O, was isolated from the condensation reaction of quinoline-2-carbaldehyde with 4-amino-4H-1,2,4-triazole. The Schiff base mol-ecule adopts an E configuration about the C=N bond and is approximately planar, with a dihedral angle between the quinoline ring system and the 1,2,4-triazole ring of 12.2 (1)°. In the crystal, one water mol-ecule bridges two Schiff base mol-ecules via O-H⋯N hydrogen bonds. The Schiff base mol-ecules are inter-connected by π-π stacking inter-actions [centroid-centroid distances of 3.7486 (7) and 3.9003 (7) Å] into columns along [10].

Proton Transport through E. coli CLC Chloride/Proton Antiporter in the Presence of Bound Fluoride

A prototypical CLC antiporter from E. coli, EcCLC, regulates the influx of Cl− and efflux of H+ across membranes. Interestingly, it does not transport F-, even though F- has a smaller radius than Cl-. Here we apply multiscale quantum-mechanical/molecular-mechanical (QM/MM) simulations to study H+ migration via the Grotthuss mechanism through the transmembrane domain of EcCLC with F− present in the central binding site. Our preliminary data suggest that the F- does not prevent the protonation of the external gating residue E148, which rotates inward into the pore to receive the migrating H+. However, the protonated E148 is stabilized by F- in the pore through hydrogen-bonding interactions via 0-2 bridging water molecules. Some trajectories even show back and forth exchanges of H+ between the F- and E148. This picture differs significantly from our previous simulations of H+ transfer in the presence of a bound Cl-, where such strong interactions are not found. These strong interactions imply that it is difficult to separate the F- and protonated E148, therefore disrupting the antiporter operating cycle. Our results agree well with the “lock down” mechanism previously proposed by Miller and coworkers based on experiments (Lim, et al. Nat. Chem. Biol. 2013, 9, 721-725).

Advances in the Treatment of Explicit Water Molecules in Docking and Binding Free Energy Calculations.

The inclusion of direct effects mediated by water during the ligandreceptor recognition is a hot-topic of modern computational chemistry applied to drug discovery and development. Docking or virtual screening with explicit hydration is still debatable, despite the successful cases that have been presented in the last years. Indeed, how to select the water molecules that will be included in the docking process or how the included waters should be treated remain open questions. In this review, we will discuss some of the most recent methods that can be used in computational drug discovery and drug development when the effect of a single water, or of a small network of interacting waters, needs to be explicitly considered. Here, we analyse the software to aid the selection, or to predict the position, of water molecules that are going to be explicitly considered in later docking studies. We also present software and protocols able to efficiently treat flexible water molecules during docking, including examples of applications. Finally, we discuss methods based on molecular dynamics simulations that can be used to integrate docking studies or to reliably and efficiently compute binding energies of ligands in presence of interfacial or bridging water molecules. Software applications aiding the design of new drugs that exploit water molecules, either as displaceable residues or as bridges to the receptor, are constantly being developed. Although further validation is needed, workflows that explicitly consider water will probably become a standard for computational drug discovery soon.

One-pot concomitant preparation of two copper(II) coordination polymers with different configurations of bridging bithiophene ligands.

By employing the conjugated bithiophene ligand 5,5'-bis(1H-imidazol-1-yl)-2,2'-bithiophene (bibp), which can exhibit trans and cis conformations, two different CuII coordination polymers, namely, poly[[μ-5,5'-bis(1H-imidazol-1-yl)-2,2'-bithiophene-κ2N:N'](μ2-4,4'-oxydibenzoato-κ2O:O')copper(II)], [Cu(C14H8O5)(C14H10N4S2)]n or [Cu(bibp)(oba)]n, (I), and catena-poly[μ-aqua-bis[μ-5,5'-bis(1H-imidazol-1-yl)-2,2'-bithiophene-κ2N:N']bis(μ3-4,4'-oxydibenzoato)-κ3O:O':O'';κ4O:O',O'':O'-dicopper(II)], [Cu2(C14H8O5)2(C14H10N4S2)(H2O)]n or [Cu2(bibp)(oba)2(H2O)]n, (II), have been prepared through one-pot concomitant crystallization and characterized by single-crystal X-ray diffraction, IR spectroscopy, elemental analysis, powder X-ray diffraction (PXRD) and thermogravimetric (TG) analysis. Single-crystal X-ray diffraction indicates that the most interesting aspect of the structure is the existence of sole trans and cis conformations of the bibp ligand in a single net of (I) and (II), respectively. Compound (I) displays a threefold interpenetrating three-dimensional framework with a 4-connected {65.8} cds topology, whereas (II) features a one-dimensional chain structure. In the crystal of (II), the polymeric chains are further extended through C-H...O hydrogen bonds and C-H...π interactions into a three-dimensional supramolecular architecture. In addition, strong intramolecular O-H...O hydrogen bonds formed between the bridging water molecules and the carboxylate O atoms improve the stability of the framework of (II). Furthermore, solid-state UV-Vis spectroscopy experiments show that compounds (I) and (II) exhibit optical band gaps which are characteristic for optical semiconductors, with values of 2.70 and 2.26 eV, respectively.

Luminescent vapochromic single crystal to single crystal transition in one-dimensional coordination polymer featuring the first Cu(i) dimer bridged by an aqua ligand

Vapochromic luminescence caused by included solvent mobility is observed in reversible single-crystal to single-crystal (SC–SC) transitions in a one-dimensional coordination polymer bearing the first reported water molecule bridging two Cu(i) ions.

Synthesis, crystal structure and bovine serum albumin–binding studies of a new Cd(II) complex incorporating 2,2′-(propane-1,3-diyl)bis(1H-imidazole-4,5-dicarboxylate)

A new Cd(II) complex, [Cd(H4pbidc)(H2O)] n (1), incorporating 2,2′-(propane-1,3-diyl)bis(1H- imidazole-4,5-dicarboxylic acid) (H6pbidc) was synthesized and characterized by elemental analysis, infrared spectra and X-ray single-crystal diffraction. In complex 1, each Cd(II) ion is hepta-coordinated, showing a significantly distorted pentagonal-bipyramidal coordination environment. Adjacent Cd(II) ions are alternately joined through two carboxylate oxygen atoms and two bridging water molecules resulting in a one-dimensional chain structure. In the solid state, adjacent chains are further linked by hydrogen bonds, forming a three-dimensional supramolecular architecture. Meanwhile, the interactions of complex 1 with bovine serum albumin were analysed by fluorescence measurements under physiological conditions. The results indicated that the fluorescence intensity of bovine serum albumin was decreased considerably upon the addition of complex 1 through a static quenching mechanism with formation of one binding site. The negative values of the thermodynamic parameters including enthalpy change (Δ H), entropy change (Δ S) and Gibbs free energy change (Δ G) showed that hydrogen bonding and van der Waals forces were the main interactions in the binding of complex 1 to bovine serum albumin, and the binding process is spontaneous in thermodynamics.

Oxybis(ethane-1,2-diyl)]bis(dimethylammonium) octamolybdate dihydrate

The title compound, (C8H22N2O)2[Mo8O26]·H2O, (cis-H2 L)2[β-Mo8O26]·H2O, where L = (bis[2-N,N-dimethylamino)ethyl] ether), was synthesized from bis[2-(dimethylamino)ethyl] ether and MoO3 under solvothermal conditions and characterized by multinuclear NMR and single-crystal X-ray diffraction techniques. The structure displays two [oxybis(ethane-1,2-diyl)]bis(dimethylammonium), or [cis-H2 L]2+, cations, a central [β-Mo8O26]4− anionic cluster consisting of eight distorted MoO6 octahedra, and two water molecules in their deuterated form. The central anion lies across an inversion center. The [cis-H2 L]2+ cations are hydrogen bonded to the central [β-Mo8O26]4− cluster via bridging water molecules. In the crystal, O—H...O hydrogen bonds link the components into chains along [010]. Weak C—H...O hydrogen bonds link these chains into a three-dimensional network.

Structural diversity, magnetic properties and luminescence of NiII, CoII and ZnII coordination polymers derived from 3,3'-[(5-carboxy-1,3-phenylene)bis(oxy)]dibenzoic acid and 1,10-phenanthroline.

Three novel coordination polymers (CPs), namely poly[[di-μ-aqua-bis{μ4-3,3'-[(5-carboxylato-1,3-phenylene)bis(oxy)]dibenzoato-κ5O1:O1',O3:O5:O5'}bis(1,10-phenanthroline-κ2N,N')trinickel(II)] dimethylformamide 1.5-solvate trihydrate], {[Ni3(C21H11O8)2(C12H8N2)2(H2O)2]·1.5C3H7NO·3H2O}n, (I), poly[[di-μ-aqua-bis{μ4-3,3'-[(5-carboxylato-1,3-phenylene)bis(oxy)]dibenzoato-κ5O1:O1',O3:O5:O5'}bis(1,10-phenanthroline-κ2N,N')tricobalt(II)] diethylamine disolvate tetrahydrate], {[Co3(C21H11O8)2(C12H8N2)2(H2O)2]·2C2H7N·4H2O}n, (II), and catena-poly[[aqua(1,10-phenanthroline-κ2N,N')zinc(II)]-μ-5-(3-carboxyphenoxy)-3,3'-oxydibenzoato-κ2O1:O3], [Zn(C21H12O8)(C12H8N2)(H2O)]n, (III), have been synthesized by the reaction of different metal ions (Ni2+, Co2+ and Zn2+), 3,3'-[(5-carboxy-1,3-phenylbis(oxy)]dibenzoic acid (H3cpboda) and 1,10-phenanthroline (phen) under solvothermal conditions. All the CPs were characterized by elemental analysis, single-crystal and powder X-ray diffraction, FT-IR spectroscopy and thermogravimetric analysis. Complexes (I) and (II) have isomorphous structures, featuring similar linear trinuclear structural units, in which the central NiII/CoII atom is located on an inversion centre with a slightly distorted octahedral [NiO6]/[CoO6] geometry. This comprises four carboxylate O-atom donors from two cpboda3- ligands and two O-atom donors from bridging water molecules. The terminal NiII/CoII groups are each connected to the central NiII/CoII cation through two μ1,3-carboxylate groups from two cpboda3- ligands and one water bridge, giving rise to linear trinuclear [M3(μ2-H2O)2(RCOO)4] (M = Ni2+/Co2+) secondary building units (SBUs) and the SBUs develop two-dimensional-networks parallel to the (100) plane via cpboda3- ligands with new (32·4)2(32·83·9)2(34·42.82·94·103) topological structures. Zinc complex (III) displays one-dimensional coordination chains and the five-coordinated Zn atom forms a distorted square-pyramidal [ZnO3N2] geometry, which is completed by two carboxylate O-atom donors from two distinct Hcpboda2- ligands, one O atom from H2O and two N atoms from a chelating phen ligand. Magnetically, CP (I) shows weak ferromagnetic interactions involving the carboxylate groups, and bridging water molecules between the nickel(II) ions, and CP (II) shows antiferromagnetic interactions between the Co2+ ions. The solid-state luminescence properties of CP (III) were examined at ambient temperature and the luminescence sensing of Cr2O72-/CrO42- anions in aqueous solution for (III) has also been investigated.

Synthesis, Crystal Structure, and Thermal Properties of Na5[SnS4]Cl·13H2O

Reaction of Na2S with SnCl4·5H2O in aqueous alkaline sodium hydroxide solution leads to the formation of Na5[SnS4]Cl·13H2O (1). The compound crystallizes monoclinic in space group P21/m with two formula units in the unit cell. In the crystal structure the Na+ cations are octahedrally coordinated and are linked into layers by bridging water molecules, μ3 bridging Cl– anions and μ1,1 bridging S atoms of [SnS4]4– anions. Extended hydrogen bonding interactions generate a three‐dimensional network. Investigations using differential thermoanalysis, thermogravimetry, and differential scanning calorimetry shows that upon heating in open crucibles the water can be removed leading to the formation of the anhydrate that is stable at room temperature and does not transform back into compound 1. Storage of the anhydrate in a desiccator over a water atmosphere leads first to formation of Na4SnS4·14H2O followed by crystallization of the title compound. After longer storage times NaCl appears as a second crystalline phase. If the thermal measurements are performed in a self‐produced atmosphere, compound 1 transforms partly into Na4SnS4·14H2O with an increasing amount of this phase with increasing temperature. Synthetic investigations reveal that crystallization of compound 1 sensitively depends on the water content of acetone, which is used for precipitation of 1. Reacting Na4SnS4·14H2O directly with NaCl afforded formation of complex mixtures.

Small-sized platinum nanoparticles in soil organic matter: Influence on water holding capacity, evaporation and structural rigidity

Engineered and anthropogenic nanoparticles represent a new type of pollutants. Up until now, many studies have reported its adverse effect on biota, but the potential influence on the properties and functions of environmental compartments has largely been ignored. In this work, the effect of Pt nanoparticles on the functions and properties of model soil organic matter has been studied. Using differential scanning calorimetry and molecular modeling, the effect of a wide range of 3 nm Pt nanoparticles concentrations on water holding capacity, the strength of water binding, the stability of water molecule bridges and the content of aliphatic crystallites was studied. It was found that strong hydration of the nanoparticles influences the 3D water structural network and acts as kosmotropic agents (structure-forming) in water bridges and as chaotropic agents (i.e. water destructuring) in larger water volumes. Contrarily, the interaction with soil organic matter moieties partially eliminates these effects. As a result, the 3 nm Pt nanoparticles decreased the evaporation enthalpy of water in soil organic matter and supported soil desiccation. They also increased the strength of water molecule bridges and increased the soil structural rigidity even at low concentrations. Additionally, at high concentrations, they decreased the water content in soil organic matter and induced the aliphatic moieties' crystallization. It is concluded that the small-sized Pt nanoparticles, and perhaps other types as well, may affect the local physicochemical processes in soils and may consequently contribute to enhanced evapotranspiration and deterioration of soil functions.

Improving protein–ligand binding prediction by considering the bridging water molecules in Autodock

Water plays a significant role in determining the protein–ligand binding modes, especially when water molecules are involved in mediating protein–ligand interactions, and these important water molecules are receiving more and more attention in recent years. Considering the effects of water molecules has gradually become a routine process for accurate description of the protein–ligand interactions. As a free docking program, Autodock has been most widely used in predicting the protein–ligand binding modes. However, whether the inclusion of water molecules in Autodock would improve its docking performance has not been systematically investigated. Here, we incorporate important bridging water molecules into Autodock program, and systematically investigate the effectiveness of these water molecules in protein–ligand docking. This approach was evaluated using 18 structurally diverse protein–ligand complexes, in which several water molecules bridge the protein–ligand interactions. Different treatment of water molecules were tested by using the fixed and rotatable water molecules, and a considerable improvement in successful docking simulations was found when including these water molecules. This study illustrates the necessity of inclusion of water molecules in Autodock docking, and emphasizes the importance of a proper treatment of water molecules in protein–ligand binding predictions.

Structure and Dynamics of Collagen Hydration Water from Molecular Dynamics Simulations: Implications of Temperature and Pressure.

Dynamics of water molecules in hydrated collagen plays an important role in determining the structural and functional properties of collagenous tissues. Experimental results suggest that collagen-bridging water molecules exhibit dynamic and thermodynamic properties of one-dimensional ice. However, molecular dynamics (MD) studies performed to date have failed to identify icelike water bridges. It has been hypothesized that this discrepancy is due to the experimental measurements and computational MD analysis having been performed on very different systems: complete tissues with large-scale collagen fiber assemblies and individual tropocollagen fragments, respectively. In this work, we explore ways of emulating a tissuelike macromolecular environment in MD simulations of hydrated collagen without increasing the size of the system to computationally prohibitive levels. We have investigated the effects of temperature and pressure on the dynamics of a small hydrated tropocollagen fragment. The occupancy and bond energies of interchain hydrogen bonds were relatively insensitive to temperature, suggesting that they play a key role in the stability of the collagen triple helix. The lifetimes of water bridges lengthened with decreasing temperature, but even at 280 K, no bridging water molecules exhibited icelike dynamics. We discuss the implications of these findings for the ability to emulate tissuelike conditions in hydrated collagen.

Predicting Positions of Bridging Water Molecules in Nucleic Acid-Ligand Complexes.

Over the past two decades, interests in DNA and RNA as drug targets have been growing rapidly. Following the trends observed with protein drug targets, computational approaches for drug design have been developed for this new class of molecules. Our efforts toward the development of a universal docking program, Fitted, led us to focus on nucleic acids. Throughout the development of this docking program, efforts were directed toward displaceable water molecules which must be accurately located for optimal docking-based drug discovery. However, although there is a plethora of methods to place water molecules in and around protein structures, there is, to the best of our knowledge, no such fully automated method for nucleic acids, which are significantly more polar and solvated than proteins. We report herein a new method, Splash'Em (Solvation Potential Laid around Statistical Hydration on Entire Macromolecules) developed to place water molecules within the binding cavity of nucleic acids. This fast method was shown to have high agreement with water positions in crystal structures and will therefore provide essential information to medicinal chemists.

MD Simulation Investigation on the Binding Process of Smoke-Derived Germination Stimulants to Its Receptor.

Karrikins (KARs) are a class of smoke-derived seed germination stimulants with great significance in both agriculture and plant biology. By means of direct binding to the receptor protein KAI2, the compounds can initiate the KAR signal transduction pathway, hence triggering germination of the dormant seeds in the soil. In the research, several molecular dynamics (MD) simulation techniques were properly integrated to investigate the binding process of KAR1 to KAI2 and reveal the details of the whole binding event. The calculated binding free energy, -7.00 kcal/mol, is in good agreement with the experimental measurement, -6.83 kcal/mol. The obtained PMF profile indicates the existence of three intermediate states in the binding process. The analysis of the simulation trajectories demonstrates that, in the intermediate structures, KAR1 is stabilized by some hydrophobic residues (Phe26, Phe134, Leu142, Trp153, Phe157, Leu160, Phe194), along with several bridging water molecules, and meanwhile, the significant shifting occurs in the local conformation of the protein as the ligand's binding. A series of the residues (Gln141-Phe157) on the so-called "cap domain" are proposed to be responsible for capturing the ligand at the initial stage of the binding. Besides, the changes of the ligand's poses are also quantitatively characterized by the proper choice of the coordinate system. Our work will contribute to the more penetrating understanding of the ligand binding process and the receptor affinity difference between several members in the KAR family and help design new, more effective germination stimulants.