Molecular Graphics (molecular + graphics)

Distribution by Scientific Domains


Selected Abstracts


QSAR of Progestogens: Use of a Priori and Computed Molecular Descriptors and Molecular Graphics

MOLECULAR INFORMATICS, Issue 4 2003
Rudolf Kiralj
Abstract Quantitative Structure-Activity Relationship (QSAR) study of two sets of oral progestogens was carried out by using Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA) and Partial Least Squares (PLS). A priori, computed (at DFT 6-31G** level) and molecular graphics and modeling descriptors were employed. Molecular graphics and modeling studies of crystal structures of complexes progesterone receptor (PR)-progesterone, Fab,-progesterone and PR-metribolone have been performed. QSAR of progestogens is a three-dimensional phenomenon (over 96% of information is explained by the first three Principal Components), which can be, although it exhibits significant non-linearity, treated well with linear methods such as PLS. Progestogen activity depends primarily on double bond contents and resonance effects which define the skeletal conformation, and also on substituent characteristics (size, conformational and electronic properties). Sterical relationships between a substituent at C6(sp2) or C6(sp3)-, and sulfur atom from Met 801 residue of PR are important for progesterone binding to the protein and can be quantified. Basically the same was observed for substituents at ,-C10 with respect to residue Met759. [source]


Artemisinin Derivatives with Antimalarial Activity against Plasmodium falciparum Designed with the Aid of Quantum Chemical and Partial Least Squares Methods

MOLECULAR INFORMATICS, Issue 8 2003

Abstract Artemisinin derivatives with antimalarial activity against Plasmodium falciparum resistant to mefloquine are designed with the aid of Quantum Chemical and Partial Least Squares Methods. The PLS model with three principal components explaining 89.55% of total variance, Q2=0.83 and R2=0.92 was obtained for 14/5 molecules in the training/external validation set. The most important descriptors for the design of the model were one level above the lowest unoccupied molecular orbital energy (LUMO+1), atomic charges in atoms C9 and C11 (Q9) and (Q11) respectively, the maximum number of hydrogen atoms that might make contact with heme (NH) and RDF030,m (a radial distribution function centered at 3.0, interatomic distance and weighted by atomic masses). From a set of ten proposed artemisinin derivatives, a new compound (26), was predicted with antimalarial activity higher than the compounds reported in literature. Molecular graphics and modeling supported the PLS results and revealed heme-ligand and protein-ligand stereoelectronic relationships as important for antimalarial activity. The most active 26 and 29 in the prediction set possess substituents at C9 able to extend to hemoglobin exterior, what determines the high activity of these compounds. [source]


QSAR of Progestogens: Use of a Priori and Computed Molecular Descriptors and Molecular Graphics

MOLECULAR INFORMATICS, Issue 4 2003
Rudolf Kiralj
Abstract Quantitative Structure-Activity Relationship (QSAR) study of two sets of oral progestogens was carried out by using Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA) and Partial Least Squares (PLS). A priori, computed (at DFT 6-31G** level) and molecular graphics and modeling descriptors were employed. Molecular graphics and modeling studies of crystal structures of complexes progesterone receptor (PR)-progesterone, Fab,-progesterone and PR-metribolone have been performed. QSAR of progestogens is a three-dimensional phenomenon (over 96% of information is explained by the first three Principal Components), which can be, although it exhibits significant non-linearity, treated well with linear methods such as PLS. Progestogen activity depends primarily on double bond contents and resonance effects which define the skeletal conformation, and also on substituent characteristics (size, conformational and electronic properties). Sterical relationships between a substituent at C6(sp2) or C6(sp3)-, and sulfur atom from Met 801 residue of PR are important for progesterone binding to the protein and can be quantified. Basically the same was observed for substituents at ,-C10 with respect to residue Met759. [source]


Integrin ,IIb,3:ligand interactions are linked to binding-site remodeling

PROTEIN SCIENCE, Issue 8 2006
Roy R. Hantgan
Abstract This study tested the hypothesis that high-affinity binding of macromolecular ligands to the ,IIb,3 integrin is tightly coupled to binding-site remodeling, an induced-fit process that shifts a conformational equilibrium from a resting toward an open receptor. Interactions between ,IIb,3 and two model ligands,echistatin, a 6-kDa recombinant protein with an RGD integrin-targeting sequence, and fibrinogen's ,-module, a 30-kDa recombinant protein with a KQAGDV integrin binding site,were measured by sedimentation velocity, fluorescence anisotropy, and a solid-phase binding assay, and modeled by molecular graphics. Studying echistatin variants (R24A, R24K, D26A, D26E, D27W, D27F), we found that electrostatic contacts with charged residues at the ,IIb/,3 interface, rather than nonpolar contacts, perturb the conformation of the resting integrin. Aspartate 26, which interacts with the nearby MIDAS cation, was essential for binding, as D26A and D26E were inactive. In contrast, R24K was fully and R24A partly active, indicating that the positively charged arginine 24 contributes to, but is not required for, integrin recognition. Moreover, we demonstrated that priming,i.e., ectodomain conformational changes and oligomerization induced by incubation at 35C with the ligand-mimetic peptide cHarGD,promotes complex formation with fibrinogen's ,-module. We also observed that the ,-module's flexible carboxy terminus was not required for ,IIb,3 integrin binding. Our studies differentiate priming ligands, which bind to the resting receptor and perturb its conformation, from regulated ligands, where binding-site remodeling must first occur. Echistatin's binding energy is sufficient to rearrange the subunit interface, but regulated ligands like fibrinogen must rely on priming to overcome conformational barriers. [source]


Lesson plan for protein exploration in a large biochemistry class,

BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, Issue 5 2003
David W. Honey
Abstract The teaching of structural concepts plays a prominent role in many chemistry and biology courses. When it comes to macromolecular systems, a thorough understanding of noncovalent interactions lays a strong foundation for students to understand such things as protein folding, the formation of protein-ligand complexes, and the melting of the DNA double helix. The incorporation of computer-based molecular graphics into the biochemistry curriculum has given students unique opportunities in visualizing the structure of biological molecules and recognizing the subtle aspects of noncovalent interactions. This report describes a series of visualization-based assignments developed to facilitate protein exploration in a large biochemistry class. A large enrollment can present special challenges for students to benefit from hands-on use of visualization software. Three of the assignments are described in detail along with a description of an on-line teaching tool used to manage the assignments and to coordinate the student groups participating in these exercises. [source]