Configurational Entropy Components and Their Contribution to Biomolecular Complex Formation.
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ABSTRACT:
SUBMITTER: Fleck M
PROVIDER: S-EPMC9251725 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The HIV-1 gp120/CD4 interaction shows a large, unprecedented entropy/enthalpy compensation, with the capacity to fine-tune recognition over a broad range of affinity. The intermolecular interaction involves stable hydrophobic contacts with a unique protruding CD4-Phe43 structure surrounded by an intermolecular hydrogen-bond network that covers the hemisphere of the CD4 D1 domain. We have applied a heuristic formula based on the covariance matrix of atom-positional fluctuations to assess the configurational entropy of the gp120/CD4 complex at different levels. The system was dissected into various subsets of atoms to evaluate the entropic contributions of different functional elements. By combining the trajectories of the free and complex forms, further insight into the conformational sampling was extracted. Despite the limited sampling time of 10 ns, the theoretically derived changes in configurational entropy are in fair agreement with the experimentally determined data. The simultaneous evaluation of different interaction modes through a decomposition approach is only feasible with the knowledge of the atomic trajectory of the system. The configurational entropy analysis in terms of combined trajectories presented here shall potentially provide accurate estimations of thermodynamic properties of biomolecules given sufficient sampling of conformational space.
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Project description:Configurational entropy is an important parameter in amorphous systems. It is involved in the thermodynamic considerations, plays an important role in the molecular mobility calculations through its appearance in the Adam-Gibbs equation and provides information on the solubility increase of an amorphous form compared to its crystalline counterpart. This paper presents a calorimetric method which enables the scientist to quickly determine the values for the configurational entropy at any temperature and obtain the maximum of information from these measurements.
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Project description:The thermodynamics of disordering in Cu3Au have been investigated by measuring the heat capacity of samples with different degrees of long- and short-range order between T = 5 and 720 K using relaxation and differential scanning calorimetry. The heat capacities of L12-ordered and fcc-disordered samples show similar behaviour at low temperatures (<300 K). They deviate positively from the linear combination of the end-member heat capacities between ∼30 and 160 K. However, small differences between the two samples exist, as the disordered sample has a larger heat capacity producing a vibrational entropy of disordering of ∼0.05 R. At temperatures higher than 300 K, the heat capacity of the ordered sample shows a prominent lambda-type anomaly at 675 K due to the diffusive L12-fcc phase transition. When starting these measurements with disordered samples, ordering effects are observed between 400 and 620 K, and the disordering reaction is observed at 660 K. Evaluation of the data gives an enthalpy and entropy of disordering at 683 K of 2.0 kJ mol-1 and 0.39 R, respectively. However, these values increase with increasing temperature, thereby reducing the short-range order. Because the vibrational and configurational disordering effects become active at different temperature regimes, i.e., the vibrational effects at low temperatures (T ≪ 300 K) and the sum of both effects at higher temperatures (T > 300 K), they have been successfully separated.
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Project description:Estimation of configurational entropy from molecular dynamics trajectories is a difficult task which is often performed using quasi-harmonic or histogram analysis. An entirely different approach, proposed recently, estimates local density distribution around each conformational sample by measuring the distance from its nearest neighbors. In this work we show this theoretically well grounded the method can be easily applied to estimate the entropy from conformational sampling. We consider a set of systems that are representative of important biomolecular processes. In particular: reference entropies for amino acids in unfolded proteins are obtained from a database of residues not participating in secondary structure elements;the conformational entropy of folding of β2-microglobulin is computed from molecular dynamics simulations using reference entropies for the unfolded state;backbone conformational entropy is computed from molecular dynamics simulations of four different states of the EPAC protein and compared with order parameters (often used as a measure of entropy);the conformational and rototranslational entropy of binding is computed from simulations of 20 tripeptides bound to the peptide binding protein OppA and of β2-microglobulin bound to a citrate coated gold surface. This work shows the potential of the method in the most representative biological processes involving proteins, and provides a valuable alternative, principally in the shown cases, where other approaches are problematic.
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