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HIV Integrase Inhibitors
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Only two studies have been reported using the 4D-QSAR approach. In the first study, Iyer and Hopfinger (2007) used 4D fingerprints to capture the 3D shape and conformation of molecules without the constraints of alignment, as well as information about molecular flexibility and conformational entropy. The authors mentioned that 4D descriptors are abstract and do not lead to precise chemical interpretation. However, it seemed that even if 4D descriptors could not provide any mechanistic interpretations, these models could be used as a virtual screening tool to identify potentially active novel compounds for synthesis. In the second study, de Melo and Ferreira (2012) derived a 4D-QSAR model for 85 IN strand transfer inhibitors with a DKA substructure using a new approach named LQTA-QSAR. This was comparable to some 2D-and 3D-QSAR models developed for other classes of DKA derivatives and was able to provide mechanistic interpretation.
Polymer Adsorption: Fundamentals
Published in E. Desmond Goddard, James V. Gruber, Principles of Polymer Science and Technology in Cosmetics and Personal Care, 1999
E. Desmond Goddard, James V. Gruber
For any spontaneous process to occur chemical thermodynamics tells us that there must be a lowering of the free energy, ΔG, of the system. The driving force for polymer adsorption is thus the competition between the net energy change on adsorption (enthalpy of adsorption), the loss of conformational entropy of the adsorbed polymer, and the gain in entropy of solvent molecules released from the surface and polymer upon adsorption.
High Mobility Group Proteins: Purification, Properties, and Amino Acid Sequence Comparisons
Published in Isaac Bekhor, Carol J. Mirell, C. C. Liew, Progress in Nonhistone Protein Research, 1985
Gerald R. Reeck, David C. Teller
The formation of a complex between one of these HMG proteins and DNA would result in the system losing a great deal of configurational entropy since the portion of the protein that binds to the DNA would be restricted in its conformation in the complex and largely unrestricted when the protein is not bound. Configurational entropy would therefore strongly favor dissociation. The loss in configurational entropy upon binding is probably minimized in these HMG proteins by the high proline content of their DNA-binding regions. The covalent bond between the Cα and the N atoms of proline would allow far less conformational freedom in the DNA-binding regions than the same regions would have if alanine, for example, were substituted for every proline. Since the unstructured DNA-binding regions of some of the histones, particularly H1 and H5, are similarly rich in proline, this may be a frequently used strategy in DNA-binding polypeptides that lack defined three-dimensional structure. It is also worth noting that a protein such as these HMG proteins, which lack organized folding and for which configurational entropy strongly favors dissociation, must have more lysine and arginine residues in their DNA-binding regions than would be required to achieve equally tight binding in other DNA-binding proteins that have similar three-dimensional structures when bound to DNA and when not bound to DNA. This would ensure that that conformation which binds to DNA binds sufficiently tightly to more than offset the strong effect of conformational entropy to promote dissociation.
Kinetic and structural studies on the interactions of Torpedo californica acetylcholinesterase with two donepezil-like rigid analogues
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Rosanna Caliandro, Alessandro Pesaresi, Luca Cariati, Antonio Procopio, Manuela Oliverio, Doriano Lamba
The AutoDock semi-empirical force field includes intramolecular terms, a “full” desolvation model, and also considers directionality in hydrogen bonds. The conformational entropy is calculated from the sum of the torsional degrees of freedom. Water molecules are not modeled explicitly though, but pair-wise atomic terms are used to estimate the water contribution (dispersion/repulsion, hydrogen bonding, electrostatics, and desolvation), where weights are added for calibration (based on experimental data). The theoretical protein-ligand binding energy ΔGb includes the calculation of i) the energy of ligand and protein in the unbound state; ii) the energy of the protein-ligand complex. Then the difference is computed: ΔGb= (VboundL-L – VunboundL-L) + (VboundP-P − VunboundP-P) + (VboundP-L − VunboundP-L+ΔSconf) where P refers to the protein, L refers to the ligand, V are the pair-wise evaluations (see above) and ΔSconfdenotes the loss of conformational entropy upon binding.56
Thermodynamic profiling for fragment-based lead discovery and optimization
Published in Expert Opinion on Drug Discovery, 2020
György G. Ferenczy, György M. Keserű
A part of conformational entropy decrease upon ligand binding originates from the more restricted variation of torsion angles in the complex compared to the solvated ligand and protein. The loss of conformational entropy is estimated to be around 3 kJ/mol at 300 K for each rotatable bond fixed in the complex [22]. The association of two species, the protein and the ligand, results in a loss of rigid body translational and rotational entropy and its estimated magnitude is around 15–20 kJ/mol at 300 K [23]. These values, however, are crude estimations and the actual magnitude of the entropy loss is affected by the flexibility of the complex; entropy may be associated with the new vibrational modes of the complex.
Increasing the stability of Lumbricus terrestris erythrocruorin via poly(acrylic acid) conjugation
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Kyle Spivack, Matthew Tucker, Devon Zimmerman, Matthew Nicholas, Osheiza Abdulmalik, Noelle Comolli, Jacob Elmer
In addition to increasing its size, cross-linking LtEc with PAA also significantly increased its structural and thermal stability (ΔTm = +5 °C for LP and ΔTm = +10 °C for LPE). This increase in melting temperature can be attributed to the formation of new covalent bonds between LtEc, PAA, and EDA that decrease the conformational entropy of the unfolded peptide. Consequently, the magnitude of the change in Gibb’s free energy during the folding/unfolding process increases, causing a subsequent increase in Tm.