Projects / Programmes
Hydrogen bonding around apolar solutes: origin of the hydrophobic effect
| Code |
Science |
Field |
Subfield |
| 1.04.01 |
Natural sciences and mathematics |
Chemistry |
Phyisical chemistry |
| Code |
Science |
Field |
| P400 |
Natural sciences and mathematics |
Physical chemistry |
| Code |
Science |
Field |
| 1.04 |
Natural Sciences |
Chemical sciences |
hydrophobic effect, atomistic simulations, ab-initio and classical MD, vibrational spectroscpy, NMR, neutron scattering, force-field parametrization
Researchers (10)
Organisations (2)
Abstract
Despite the intensive research hydrophobicity is far from being understood completely at the fundamental level. This is mainly because the hydrophobic effect is associated by subtle and complex changes in the surrounding aqueous medium, which are extremely difficult to access directly by existing experimental techniques. The main focus of the proposed project will be on resolving the microscopic picture of the hydrophobic effect and its immediate consequences to the structure and dynamics of biomolecular systems, which is unequivocally one of the most important challenges in physical biochemistry. Each effort in this direction mandates finding an appropriate and solid experimental evidence of the structural and dynamical changes in hydration water, which is consistent with the theoretical predictions based on the most accurate computer simulations. To capture the solute induced differences in hydrogen bonding (HB) relative to bulk, we will first focus on the frequency shifts of the water OH stretching mode as it is known to be sensitive to the local environment. Any down-shifting (redshift) of the OH stretching frequencies detected when switching from bulk water to hydration water surrounding apolar solvents would indicate stronger HB of water in the vicinity of hydrophobic solutes.
An important goal of the project will be to establish a wider confirmation of our preliminary result indicating the existence of the strengthened water HB around solvated methane. We aim to explore the whole set of pure hydrophobic solutes, such as methane, ethane, krypton, and xenon, using vibrational spectroscopy (IR, Raman) and advanced theoretical methods over a wide range of thermodynamic parameters. Extensive ab initio molecular dynamics simulations based on recently developed DFT functionals, which have been proven to properly account for dispersive forces, will be performed on the various systems studied in parallel experimentally to provide a detailed atomistic picture of the observed effect. Structural and dynamical information of water will be derived from these experimental and theoretical studies and critically compared with the available experimental and theoretical data in order to support or refute the long disputed validity of the so called “ice-berg” hypotesis.
Along with the widely recognized central role of hydrophobic interaction in describing protein structure, folding and association, an improved water model should, in principle, enhance overall acuracy of the force fields used in the classical atomistic simulations of biomolecules. Based on the derived quantitaive relationships for hydrogen bonding around small pure hydrophobic molecules we aim to propose improvements of the standard force field parameterizations used in the classical atomistic simulations. Improved force fileds will be checked against the ability of reproducing the so-far neglected strengthening of the nearby hydrogen bonds around apolar solutes. Impact on biomolecular simulations focusing particularly on prediction of small-peptide conformations and association will be explicitly evaluated. Data on three-dimensional structures and dynamics of peptide will be obtained using vibrational and NMR spectroscopy as well as the neutron scattering techniques.
Obtaining a detailed knowledge on behavior of hydrogen bonds around hydrophobic molecules will allow to construct more efficient analytical and simple generic models for hydration of hydrophobic particles and their solvent mediated interaction. This way we will be able to assess the consequences of the proposed improvements for description of hydrophobic interaction on the self-assembly on wide range of solutes.
Significance for science
Activities within the proposed project will significantly contribute to the understanding of hydrophobic effect and its consequences, which is one of the most fundantal driving forces in molecular biophysics. Despite the intensive research the microscopic picture of hydrophobicity remains an elusive phenomenon.
The proposed improvements of the biomolecular force field should allow exploration of molecular properties at increased accuracy over a wide range of biophysical phenomena. Detailed knowledge of the molecular events in protein folding is important for understanding causes of hundreds of diseases including some of the most dreadful disorders like: Alzheimer's and Parkinson's diseases, some types of cancer, type II diabetes, cystic fibrosis, transmissible prion diseases (“mad cow” disease), etc.
Significance for the country
The proposed research project is original and is based on our previously published research.
The results of this research have been published in the scientific journals with very high impact
factors (Nature, Proc. Natl. Acad. Sci. USA; J. Am. Chem. Soc.; Phys. Rev. Lett.), which shows that our research is of high quality. With these results we promote Slovenian science. The research team is experienced, highly qualified and have all the necessary equipment to successfully achieve the goals of proposed research project.
Implementation of modern methods of computer simulations of biomolecular systems, NMR and
vibrational spectroscopy is in our national interest. The development of these techniques is
crucial for technological progress of some branches in Slovenia.
Young researchers will participate in the research. Young researchers will be acquiring important
knowledge required for realization of basic research project as well as development project in particular in pharmaceutical industry.
Most important scientific results
Interim report,
final report
Most important socioeconomically and culturally relevant results
Interim report,
final report
