A5030625494- Metal-Catalyzed Oxygenation Mechanisms
- Metalloenzymes and iron-sulfur proteins
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Electrocatalysts for Energy Conversion
- Spectroscopy and Quantum Chemical Studies
- Advanced Chemical Physics Studies
- Photosynthetic Processes and Mechanisms
- Porphyrin Metabolism and Disorders
- Hemoglobin structure and function
- Ammonia Synthesis and Nitrogen Reduction
- Metal complexes synthesis and properties
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Hydrogen Storage and Materials
- Crystallography and molecular interactions
- Computational Drug Discovery Methods
- Galectins and Cancer Biology
- Porphyrin and Phthalocyanine Chemistry
- Enzyme Catalysis and Immobilization
- Free Radicals and Antioxidants
- Enzyme-mediated dye degradation
- Advanced Glycation End Products research
- Glycosylation and Glycoproteins Research
- Mass Spectrometry Techniques and Applications
Lund University
2016-2025
Shanxi University
2024
Institute of Theoretical Physics
1999-2020
European Spallation Source
2019
Donostia International Physics Center
2017
University of the Basque Country
2017
Shahid Beheshti University
2017
Getinge (Sweden)
2015
University of Manchester
2012-2014
SARomics Biostructures (Sweden)
2010
Four methods for deriving partial atomic charges from the quantum chemical electrostatic potential (CHELP, CHELPG, Merz-Kollman, and RESP) have been compared critically evaluated. It is shown strongly depend on how where points are selected. Two alternative suggested to avoid arbitrariness in point-selection schemes van der Waals exclusion radii: CHELP-BOW, which also estimates potential, but with that Boltzmann-weighted after their occurrence actual simulations using energy function of...
The free energy of binding between avidin and seven biotin analogues has been calculated with the molecular mechanics Poisson−Boltzmann surface area (MM/PBSA) method. We have studied how force field method to generate geometries affect energies. Four different fields were compared, but we saw no significant difference in results. However, mixing used for geometry generation calculations is not recommended. In dynamics simulations, explicit water molecules must be used, size simulated system...
The copper coordination geometry in the blue proteins plastocyanin, nitrite reductase, cucumber basic protein, and azurin has been studied by combined density functional (B3LYP) molecular mechanical methods. Compared to quantum chemical vacuum calculations, a significant improvement of is seen (toward experimental structures) not only for dihedral angles ligands but also bond lengths around ion. flexible Cu–SMet well reproduced oxidized structures, whereas it too long some reduced complexes...
This article investigates the performance of five commonly used density functionals, B3LYP, BP86, PBE0, PBE, and BLYP, for studying diatomic molecules consisting a first row transition metal bonded to H, F, Cl, Br, N, C, O, or S. Results have been compared with experiment wherever possible. Open-shell configurations are found more often in order PBE0>B3LYP>PBE∼BP86>BLYP. However, on average, 58 63 spins correctly predicted by any functional, only small differences. BP86...
Rational drug design is predicated on knowledge of the three-dimensional structure protein−ligand complex and thermodynamics ligand binding. Despite fundamental importance both enthalpy entropy in driving binding, role conformational rarely addressed design. In this work, we have probed its relative contribution to free energy binding carbohydrate recognition domain galectin-3. Using a combination NMR spectroscopy, isothermal titration calorimetry, X-ray crystallography, characterized three...
Abstract The molecular mechanics/generalized Born surface area (MM/GBSA) method has been investigated with the aim of achieving a statistical precision 1 kJ/mol for results. We studied binding seven biotin analogues to avidin, taking advantage fact that protein is tetramer four independent sites, which should give same estimated affinities. show it not enough use single long simulation (10 ns), because standard error such calculation underestimates difference between sites. Instead, better...
We have studied the convergence of QM/MM calculations with respect to size QM system. study a proton transfer between first-sphere cysteine ligand and second-sphere histidine group in [Ni,Fe] hydrogenase use 446-atom model protein, treated purely methods as reference. tested 12 different ways redistribute charges close junctions (to avoid overpolarization system), but once are moved away from active site, there is little need charges. 13 variants approaches, including two schemes correct...
We have performed a systematic study of the entropy term in MM/GBSA (molecular mechanics combined with generalized Born and surface-area solvation) approach to calculate ligand-binding affinities. The entropies are calculated by normal-mode analysis harmonic frequencies from minimized snapshots molecular dynamics simulations. For computational reasons, these calculations normally been on truncated systems. studied binding eight inhibitors blood clotting factor Xa, nine ligands ferritin, two...
We have used density functional methods to calculate fully relaxed potential energy curves of the seven lowest electronic states during binding O2 a realistic model ferrous deoxyheme. Beyond Fe–O distance ∼2.5 Å, we find broad crossing region with five within 15 kJ/mol. The almost parallel surfaces strongly facilitate spin inversion, which is necessary in reaction heme (deoxyheme quintet and triplet, whereas oxyheme singlet). Thus, despite small spin-orbit coupling heme, transition...
The recognition of carbohydrates by proteins is a fundamental aspect communication within and between living cells. Understanding the molecular basis carbohydrate–protein interactions prerequisite for rational design synthetic ligands. Here we report high- to ultra-high-resolution crystal structures carbohydrate domain galectin-3 (Gal3C) in ligand-free state (1.08 Å at 100 K, 1.25 298 K) complex with lactose (0.86 Å) or glycerol (0.9 Å). These reveal striking similarities positions water...
We have modified the popular MM/PBSA or MM/GBSA approaches (molecular mechanics for a biomolecule, combined with Poisson−Boltzmann generalized Born electrostatic and surface area nonelectrostatic solvation energy) by employing instead statistical-mechanical, three-dimensional molecular theory of (also known as 3D reference interaction site model, 3D-RISM-KH) coupled dynamics (Blinov, N.; et al. Biophys. J. 2010; Luchko, T.; Chem. Theory Comput. 2010). Unlike PBSA GBSA semiempirical...
Particulate methane monooxygenase (pMMO) is one of the few enzymes that can activate methane. The metal content this enzyme has been highly controversial, with suggestions a dinuclear Fe site or mono-, di-, trinuclear Cu sites. Crystal structures have shown mono- site, but resolution was low and geometry unusual. We employed quantum refinement (crystallographic enhanced quantum-mechanical calculations) to improve structure active site. compared number different geometries, in some cases more...
Abstract Crystallography and quantum mechanics have always been tightly connected because reliable mechanical models are needed to determine crystal structures. Due this natural synergy, nowadays accurate distributions of electrons in space can be obtained from diffraction scattering experiments. In the original definition crystallography (QCr) given by Massa, Karle Huang, direct extraction wavefunctions or density matrices measured intensities reflections or, conversely, ad hoc calculations...
There is no fundamental difference in enthalpy–entropy compensation between dispersion and electrostatics or quantum molecular mechanics.
We have critically examined and compared various ways to obtain standard harmonic molecular mechanics (MM) force-field parameters for metal sites in proteins, using the 12 most common Zn(2+) as test cases. show that parametrization of is hard treat with automatic methods. The choice method a compromise between speed accuracy therefore depends on intended use parameters. If site not central interest investigation, example, structural far from active site, simple fast normally enough, either...
Molecular mechanics with generalised Born and surface area solvation (MM/GBSA) is a popular method to calculate the free energy of binding ligands proteins. It involves molecular dynamics (MD) simulations an explicit solvent protein–ligand complex give set snapshots for which energies are calculated implicit solvent. This change in (explicit → implicit) would strictly require that reweighted implicit-solvent energies, normally not done. In this paper we MM/GBSA two models generated by same...
Understanding the driving forces underlying molecular recognition is of fundamental importance in chemistry and biology. The challenge to unravel binding thermodynamics into separate contributions interpret these terms. Entropic free energy are particularly difficult assess this regard. Here we pinpoint determinants differences ligand affinity carbohydrate domain galectin-3, using a combination isothermal titration calorimetry, X-ray crystallography, NMR relaxation, dynamics simulations...