dattam venkateswarlu - Academia.edu (original) (raw)
Papers by dattam venkateswarlu
Journal of the Chemical Society, Perkin Transactions 2, 1997
C 8-Oxidised purines like 7-hydro-8-oxoguanine (8OG) and 7-hydro-8-oxoadenine (8OA) are known as ... more C 8-Oxidised purines like 7-hydro-8-oxoguanine (8OG) and 7-hydro-8-oxoadenine (8OA) are known as products of oxidative DNA damage. Semiempirical molecular orbital calculations at the PM3 SCF-MO level are used to investigate the base-pairing properties of these bases in an attempt to understand their mutagenic properties. A detailed analysis of the base-pairing properties of these bases leads to an identification of the most probable pairing schemes involved in mutagenic base-mispairing. It is suggested that both bases are capable of inducing transversional as well as transitional mutations via basemispairing. The results presented are largely in consonance with available experimental reports.
Journal of computer-aided molecular design, 1998
Free-radical-induced DNA damage by ionizing radiation leads to a number of oxidized purines, of w... more Free-radical-induced DNA damage by ionizing radiation leads to a number of oxidized purines, of which 7H-8-oxoguanine (8OG) and 7H-8-oxoadenine (8OA) are predominant and known to cause an appreciable amount of cellular damage. A detailed quantum mechanical study at various levels of theory in both the gas phase and in an aqueous solution has been carried out in order to assess the tautomeric preferences of the bases. The calculated energies of various plausible tautomers suggest that at higher levels of ab initio theory with inclusion of electron correlation, the 8-keto-6-enolic form of 8-oxoguanine (8OG2) would predominate over the 6,8-diketo form (8OG1) in the gas phase whereas the 6-amino-8-keto form (8OA1) predominates over the other possible tautomers of 8-oxoadenine. Aqueous solvation, however, changes the gas-phase order for 8-oxoguanine, 8OG1 turning out to be the major tautomeric species in an aqueous medium. The estimated free energies of hydration by polarized continuum m...
Journal of the Chemical Society, Perkin Transactions 2, 1995
ABSTRACT The products of methylation at the N3-, O6- and N7-positions of guanine and at the O2- a... more ABSTRACT The products of methylation at the N3-, O6- and N7-positions of guanine and at the O2- and O4- positions of thymine are subjected to various possibilities for pairing with DNA bases, using calculations at the semiempirical PM3 SCF-MO level. It is predicted that the presence of the Watson–Crick protons in the modified bases would lead to non-mutagenic base-pairing schemes, while their absence facilitates promutagenic pairing schemes, modified guanines behaving like adenine and modified thymines like cytosine. Some degree of competition with non-mutagenic base-pairing schemes is also anticipated. Only the conformers of the O-methylated bases with the O-methyl group anti to the hydrogen bonding side furnish feasible base-mispairing schemes in the double-helical configuration. The syn conformers do not pair in the double-helical configuration. Correlation of these results with experimental and theoretically predicted Watson–Crick proton acidities for the nucleoside systems leads to the prediction that N3- and O6-methylguanines and O2 and O4-methylthymines would be promutagenic bases at biological pH, while N1-methylguanine would behave without miscoding properties. These predictions are largely confirmed by the reported experimental template properties of these modified DNA bases and are also corroborated by NMR, UV and crystallography studies on some of the modified bases considered here.
The Journal of Physical Chemistry A, 2004
ABSTRACT The X-ray crystal structure of γ-carboxyglutamic acid (Gla) domains is well-established.... more ABSTRACT The X-ray crystal structure of γ-carboxyglutamic acid (Gla) domains is well-established. These domains are stable to long all-atom simulations in explicit solvent. Here we extend a prior simulation on the Gla domain of factor VIIa, an essential vitamin K-dependent protein involved in the initiation of blood coagulation, to 20 ns in order to establish a reference point. We also subject this domain to a set of rational environmental changes using molecular dynamics techniques that accommodate long-range electrostatics accurately: (a) we move the seven bound calcium ions to >17.5 Å from any Gla residue and then simulate for 25 ns, and (b) in a separate calculation, we change all of the calcium ions to sodium ions and simulate for 20 ns. For both perturbed systems, the N-terminus chelation complex is initially greatly weakened, leading to increased motion of the ω loop (residues 1−11). In technique a, most calcium ions return to the preperturbation coordinating units within the time scale of the simulation. We track and display the sequence of calcium ion rebinding. The response of this complex, nonstandard system to the perturbations as estimated by accurate all-atom dynamics gives new details on the degree of sampling in early refolding events.
Nucleic Acids Research, 1999
The physical properties of a DNA:RNA hybrid sequence d(CCAACGTTGG)•(CCAACGUUGG) with modification... more The physical properties of a DNA:RNA hybrid sequence d(CCAACGTTGG)•(CCAACGUUGG) with modifications at the C2′-positions of the DNA strand by 2′-O-methyl (OMe) and 2′-S-methyl (SMe) groups are studied using computational techniques. Molecular dynamics simulations of SMe_DNA:RNA, OMe_DNA:RNA and standard DNA:RNA hybrids in explicit water indicate that the nature of the C2′-substituent has a significant influence on the macromolecular conformation. While the RNA strand in all duplexes maintains a strong preference for C3′-endo sugar puckering, the DNA strand shows considerable variation in this parameter depending on the nature of the C2′-substituent. In general, the preference for C3′-endo puckering follows the following trend: OMe_DNA>DNA>SMe_DNA. These results are further corroborated using ab initio methods. Both gas phase and implicit solvation calculations show the C2′-OMe group stabilizes the C3′-endo conformation while the less electronegative SMe group stabilizes the C2′-endo conformation when compared to the standard nucleoside. The macromolecular conformation of these nucleic acids also follows an analogous trend with the degree of A-form character decreasing as OMe_DNA:RNA>DNA:RNA>SMe_DNA:RNA. A structural analysis of these complexes is performed and compared with experimental melting point temperatures to explain the structural basis to improved binding affinity across this series. Finally, a possible correlation between RNase H activity and conformational changes within the minor groove of these complexes is hypothesized.
Journal of Thrombosis and Haemostasis, 2003
To cite this article: Venkateswarlu D, Duke RE, Perera L, Darden TA, Pedersen LG. An all-atom sol... more To cite this article: Venkateswarlu D, Duke RE, Perera L, Darden TA, Pedersen LG. An all-atom solution-equilibrated model for human extrinsic blood coagulation complex (sTF±VIIa±Xa): a protein±protein docking and molecular dynamics re®nement study. J Thromb Haemost 2003; 1: 2577±88.
Journal of Thrombosis and Haemostasis, 2006
Broze GJ, Forastiero R. Antiphospholipid antibodies and antibodies to tissue factor pathway inhib... more Broze GJ, Forastiero R. Antiphospholipid antibodies and antibodies to tissue factor pathway inhibitor in women with implantation failures or early and late pregnancy losses. J Thromb Haemost 2005; 3: 2587-9. 15 Backos M, Rai R, Baxter N, Chilcott IT, Cohen H, Regan L. Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. Br J Obstet Gynaecol 1999; 106: 102-7. 16 Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 1997; 314: 253-7. 17 Dolitzky M, Inbal A, Segal Y, Weiss A, Brenner B, Carp H. A randomized study of thromboprophylaxis in women with unexplained consecutive recurrent miscarriages. Fertil Steril 2006; 86: 362-6. 18 Brenner B, Hoffman R, Carp H, Dulitsky M, Younis J. Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy loss: the LIVE-ENOX study. J Thromb Haemost 2005; 3: 227-9. 19 Aharon A, Lanir N, Drugan A, Brenner B. Placental TFPI is decreased in gestational vascular complications and can be restored by maternal enoxaparin treatment. J Thromb Haemost 2005; 3: 2355-7. 20 van Ôt Veer C, Golden NJ, Kalafatis M, Mann KG. Inhibitory mechanism of the protein C pathway on tissue factor-induced thrombin generation. Synergistic effect in combination with tissue factor pathway inhibitor.
Journal of Molecular Modeling, 2002
Trocarin belongs to group D of prothrombin activators derived from snake venom of Tropidechis car... more Trocarin belongs to group D of prothrombin activators derived from snake venom of Tropidechis carinatus and is a rich non-hepatic source of Xa, the only known hepatic prothrombin activator. The structural and functional similarity with Xa makes trocarin an interesting target for exploring the structure-functional relationship with Xa. Herein we report a predicted complete three-dimensional all-atom structural model of trocarin equilibrated in explicit water using 4 ns of molecular dynamics simulation. The tertiary structure was modeled using the structure of human blood coagulation factor Xa. The conformational and structural features of trocarin are then compared with the X-ray crystal and solution simulation structures of human factor Xa. The modeled structure of trocarin has four individual domains (Gla, EGF1, EGF2 and SP) connected along the long axis with similar secondary structural elements to Xa. The simulations suggest that sodium ion binding in the serine protease domain is impaired in trocarin as compared to Xa. In contrast to Xa, for which the sodium ion forms an octahedral coordination network that brings two loop regions connecting four anti-parallel β-sheets together, we do not find a similar pattern of network in trocarin. We observe that the difference in the binding pattern of sodium ion leads to a ~2-Å "shrinkage" of the β2 strand (B2), in comparison to human Xa, as marked by a shorter distance between 189 Asp373 (S1-site residue) and 195 Ser379 (active-site residue) in the B2 strand. We propose that these differences may be linked to the experimentally observed lower amidolytic activity of trocarin as compared to Xa.
Journal of Genetics, 2011
Sorghum (Sorghum bicolor (L.) Moench) is one of the most important crops in the semiarid regions ... more Sorghum (Sorghum bicolor (L.) Moench) is one of the most important crops in the semiarid regions of the world. One of the important biotic constraints to sorghum production in India is the shoot fly which attacks sorghum at the seedling stage. Identification of the genomic regions containing quantitative trait loci (QTLs) for resistance to shoot fly and the linked markers can facilitate sorghum improvement programmes through marker-assisted selection. A simple sequence repeat (SSR) markerbased skeleton linkage map of two linkage groups of sorghum was constructed in a population of 135 recombinant inbred lines (RIL) derived from a cross between IS18551 (resistant to shoot fly) and 296B (susceptible to shoot fly). A total of 14 SSR markers, seven each on linkage groups A and C were mapped. Using data of different shoot fly resistance component traits, one QTL which is common for glossiness, oviposition and dead hearts was detected following composite interval mapping (CIM) on linkage group A. The phenotypic variation explained by this QTL ranged from 3.8%-6.3%. Besides the QTL detected by CIM, two more QTLs were detected following multi-trait composite interval mapping (MCIM), one each on linkage groups A and C for the combinations of traits which were correlated with each other. Results of the present study are novel as we could find out the QTLs governing more than one trait (pleiotropic QTLs). The identification of pleiotropic QTLs will help in improvement of more than one trait at a time with the help of the same linked markers. For all the QTLs, the resistant parent IS18551 contributed resistant alleles.
Biophysical Journal, 2002
The solution structure and dynamics of the human coagulation factor X (FX) have been investigated... more The solution structure and dynamics of the human coagulation factor X (FX) have been investigated to understand the key structural elements in the zymogenic form that participates in the activation process. The model was constructed based on the 2.3-Å-resolution x-ray crystallographic structure of active-site inhibited human FXa (PDB:1XKA). The missing ␥-carboxyglutamic acid (GLA) and part of epidermal growth factor 1 (EGF1) domains of the light chain were modeled based on the template of GLA-EGF1 domains of the tissue factor (TF)-bound FVIIa structure (PDB:1DAN). The activation peptide and other missing segments of FX were introduced using homology modeling. The full calcium-bound model of FX was subjected to 6.2 ns of molecular dynamics simulation in aqueous medium using the AMBER6.0 package. We observed significant reorientation of the serine-protease (SP) domain upon activation leading to a compact multi-domain structure. The solution structure of zymogen appears to be in a well-extended conformation with the distance between the calcium ions in the GLA domain and the catalytic residues estimated to be ϳ95 Å in contrast to ϳ83 Å in the activated form. The latter is in close agreement with fluorescence studies on FXa. The S1-specificity residues near the catalytic triad show significant differences between the zymogen and activated structures.
... Coray M. Colina 1 , Robert E. Duke 2 , Divi Venkateswarlu 3 , Lalith Perera 2 , Tom Darden 2 ... more ... Coray M. Colina 1 , Robert E. Duke 2 , Divi Venkateswarlu 3 , Lalith Perera 2 , Tom Darden 2 , and Lee G Pedersen 1 . (1) Department of Chemistry ... We performed systematic MD simulations of this complex, using the AMBER suite, for over 22 ns each at different conditions. ...
Journal of the Chemical Society, Perkin Transactions 2, 1997
C 8-Oxidised purines like 7-hydro-8-oxoguanine (8OG) and 7-hydro-8-oxoadenine (8OA) are known as ... more C 8-Oxidised purines like 7-hydro-8-oxoguanine (8OG) and 7-hydro-8-oxoadenine (8OA) are known as products of oxidative DNA damage. Semiempirical molecular orbital calculations at the PM3 SCF-MO level are used to investigate the base-pairing properties of these bases in an attempt to understand their mutagenic properties. A detailed analysis of the base-pairing properties of these bases leads to an identification of the most probable pairing schemes involved in mutagenic base-mispairing. It is suggested that both bases are capable of inducing transversional as well as transitional mutations via basemispairing. The results presented are largely in consonance with available experimental reports.
Journal of computer-aided molecular design, 1998
Free-radical-induced DNA damage by ionizing radiation leads to a number of oxidized purines, of w... more Free-radical-induced DNA damage by ionizing radiation leads to a number of oxidized purines, of which 7H-8-oxoguanine (8OG) and 7H-8-oxoadenine (8OA) are predominant and known to cause an appreciable amount of cellular damage. A detailed quantum mechanical study at various levels of theory in both the gas phase and in an aqueous solution has been carried out in order to assess the tautomeric preferences of the bases. The calculated energies of various plausible tautomers suggest that at higher levels of ab initio theory with inclusion of electron correlation, the 8-keto-6-enolic form of 8-oxoguanine (8OG2) would predominate over the 6,8-diketo form (8OG1) in the gas phase whereas the 6-amino-8-keto form (8OA1) predominates over the other possible tautomers of 8-oxoadenine. Aqueous solvation, however, changes the gas-phase order for 8-oxoguanine, 8OG1 turning out to be the major tautomeric species in an aqueous medium. The estimated free energies of hydration by polarized continuum m...
Journal of the Chemical Society, Perkin Transactions 2, 1995
ABSTRACT The products of methylation at the N3-, O6- and N7-positions of guanine and at the O2- a... more ABSTRACT The products of methylation at the N3-, O6- and N7-positions of guanine and at the O2- and O4- positions of thymine are subjected to various possibilities for pairing with DNA bases, using calculations at the semiempirical PM3 SCF-MO level. It is predicted that the presence of the Watson–Crick protons in the modified bases would lead to non-mutagenic base-pairing schemes, while their absence facilitates promutagenic pairing schemes, modified guanines behaving like adenine and modified thymines like cytosine. Some degree of competition with non-mutagenic base-pairing schemes is also anticipated. Only the conformers of the O-methylated bases with the O-methyl group anti to the hydrogen bonding side furnish feasible base-mispairing schemes in the double-helical configuration. The syn conformers do not pair in the double-helical configuration. Correlation of these results with experimental and theoretically predicted Watson–Crick proton acidities for the nucleoside systems leads to the prediction that N3- and O6-methylguanines and O2 and O4-methylthymines would be promutagenic bases at biological pH, while N1-methylguanine would behave without miscoding properties. These predictions are largely confirmed by the reported experimental template properties of these modified DNA bases and are also corroborated by NMR, UV and crystallography studies on some of the modified bases considered here.
The Journal of Physical Chemistry A, 2004
ABSTRACT The X-ray crystal structure of γ-carboxyglutamic acid (Gla) domains is well-established.... more ABSTRACT The X-ray crystal structure of γ-carboxyglutamic acid (Gla) domains is well-established. These domains are stable to long all-atom simulations in explicit solvent. Here we extend a prior simulation on the Gla domain of factor VIIa, an essential vitamin K-dependent protein involved in the initiation of blood coagulation, to 20 ns in order to establish a reference point. We also subject this domain to a set of rational environmental changes using molecular dynamics techniques that accommodate long-range electrostatics accurately: (a) we move the seven bound calcium ions to >17.5 Å from any Gla residue and then simulate for 25 ns, and (b) in a separate calculation, we change all of the calcium ions to sodium ions and simulate for 20 ns. For both perturbed systems, the N-terminus chelation complex is initially greatly weakened, leading to increased motion of the ω loop (residues 1−11). In technique a, most calcium ions return to the preperturbation coordinating units within the time scale of the simulation. We track and display the sequence of calcium ion rebinding. The response of this complex, nonstandard system to the perturbations as estimated by accurate all-atom dynamics gives new details on the degree of sampling in early refolding events.
Nucleic Acids Research, 1999
The physical properties of a DNA:RNA hybrid sequence d(CCAACGTTGG)•(CCAACGUUGG) with modification... more The physical properties of a DNA:RNA hybrid sequence d(CCAACGTTGG)•(CCAACGUUGG) with modifications at the C2′-positions of the DNA strand by 2′-O-methyl (OMe) and 2′-S-methyl (SMe) groups are studied using computational techniques. Molecular dynamics simulations of SMe_DNA:RNA, OMe_DNA:RNA and standard DNA:RNA hybrids in explicit water indicate that the nature of the C2′-substituent has a significant influence on the macromolecular conformation. While the RNA strand in all duplexes maintains a strong preference for C3′-endo sugar puckering, the DNA strand shows considerable variation in this parameter depending on the nature of the C2′-substituent. In general, the preference for C3′-endo puckering follows the following trend: OMe_DNA>DNA>SMe_DNA. These results are further corroborated using ab initio methods. Both gas phase and implicit solvation calculations show the C2′-OMe group stabilizes the C3′-endo conformation while the less electronegative SMe group stabilizes the C2′-endo conformation when compared to the standard nucleoside. The macromolecular conformation of these nucleic acids also follows an analogous trend with the degree of A-form character decreasing as OMe_DNA:RNA>DNA:RNA>SMe_DNA:RNA. A structural analysis of these complexes is performed and compared with experimental melting point temperatures to explain the structural basis to improved binding affinity across this series. Finally, a possible correlation between RNase H activity and conformational changes within the minor groove of these complexes is hypothesized.
Journal of Thrombosis and Haemostasis, 2003
To cite this article: Venkateswarlu D, Duke RE, Perera L, Darden TA, Pedersen LG. An all-atom sol... more To cite this article: Venkateswarlu D, Duke RE, Perera L, Darden TA, Pedersen LG. An all-atom solution-equilibrated model for human extrinsic blood coagulation complex (sTF±VIIa±Xa): a protein±protein docking and molecular dynamics re®nement study. J Thromb Haemost 2003; 1: 2577±88.
Journal of Thrombosis and Haemostasis, 2006
Broze GJ, Forastiero R. Antiphospholipid antibodies and antibodies to tissue factor pathway inhib... more Broze GJ, Forastiero R. Antiphospholipid antibodies and antibodies to tissue factor pathway inhibitor in women with implantation failures or early and late pregnancy losses. J Thromb Haemost 2005; 3: 2587-9. 15 Backos M, Rai R, Baxter N, Chilcott IT, Cohen H, Regan L. Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. Br J Obstet Gynaecol 1999; 106: 102-7. 16 Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 1997; 314: 253-7. 17 Dolitzky M, Inbal A, Segal Y, Weiss A, Brenner B, Carp H. A randomized study of thromboprophylaxis in women with unexplained consecutive recurrent miscarriages. Fertil Steril 2006; 86: 362-6. 18 Brenner B, Hoffman R, Carp H, Dulitsky M, Younis J. Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy loss: the LIVE-ENOX study. J Thromb Haemost 2005; 3: 227-9. 19 Aharon A, Lanir N, Drugan A, Brenner B. Placental TFPI is decreased in gestational vascular complications and can be restored by maternal enoxaparin treatment. J Thromb Haemost 2005; 3: 2355-7. 20 van Ôt Veer C, Golden NJ, Kalafatis M, Mann KG. Inhibitory mechanism of the protein C pathway on tissue factor-induced thrombin generation. Synergistic effect in combination with tissue factor pathway inhibitor.
Journal of Molecular Modeling, 2002
Trocarin belongs to group D of prothrombin activators derived from snake venom of Tropidechis car... more Trocarin belongs to group D of prothrombin activators derived from snake venom of Tropidechis carinatus and is a rich non-hepatic source of Xa, the only known hepatic prothrombin activator. The structural and functional similarity with Xa makes trocarin an interesting target for exploring the structure-functional relationship with Xa. Herein we report a predicted complete three-dimensional all-atom structural model of trocarin equilibrated in explicit water using 4 ns of molecular dynamics simulation. The tertiary structure was modeled using the structure of human blood coagulation factor Xa. The conformational and structural features of trocarin are then compared with the X-ray crystal and solution simulation structures of human factor Xa. The modeled structure of trocarin has four individual domains (Gla, EGF1, EGF2 and SP) connected along the long axis with similar secondary structural elements to Xa. The simulations suggest that sodium ion binding in the serine protease domain is impaired in trocarin as compared to Xa. In contrast to Xa, for which the sodium ion forms an octahedral coordination network that brings two loop regions connecting four anti-parallel β-sheets together, we do not find a similar pattern of network in trocarin. We observe that the difference in the binding pattern of sodium ion leads to a ~2-Å "shrinkage" of the β2 strand (B2), in comparison to human Xa, as marked by a shorter distance between 189 Asp373 (S1-site residue) and 195 Ser379 (active-site residue) in the B2 strand. We propose that these differences may be linked to the experimentally observed lower amidolytic activity of trocarin as compared to Xa.
Journal of Genetics, 2011
Sorghum (Sorghum bicolor (L.) Moench) is one of the most important crops in the semiarid regions ... more Sorghum (Sorghum bicolor (L.) Moench) is one of the most important crops in the semiarid regions of the world. One of the important biotic constraints to sorghum production in India is the shoot fly which attacks sorghum at the seedling stage. Identification of the genomic regions containing quantitative trait loci (QTLs) for resistance to shoot fly and the linked markers can facilitate sorghum improvement programmes through marker-assisted selection. A simple sequence repeat (SSR) markerbased skeleton linkage map of two linkage groups of sorghum was constructed in a population of 135 recombinant inbred lines (RIL) derived from a cross between IS18551 (resistant to shoot fly) and 296B (susceptible to shoot fly). A total of 14 SSR markers, seven each on linkage groups A and C were mapped. Using data of different shoot fly resistance component traits, one QTL which is common for glossiness, oviposition and dead hearts was detected following composite interval mapping (CIM) on linkage group A. The phenotypic variation explained by this QTL ranged from 3.8%-6.3%. Besides the QTL detected by CIM, two more QTLs were detected following multi-trait composite interval mapping (MCIM), one each on linkage groups A and C for the combinations of traits which were correlated with each other. Results of the present study are novel as we could find out the QTLs governing more than one trait (pleiotropic QTLs). The identification of pleiotropic QTLs will help in improvement of more than one trait at a time with the help of the same linked markers. For all the QTLs, the resistant parent IS18551 contributed resistant alleles.
Biophysical Journal, 2002
The solution structure and dynamics of the human coagulation factor X (FX) have been investigated... more The solution structure and dynamics of the human coagulation factor X (FX) have been investigated to understand the key structural elements in the zymogenic form that participates in the activation process. The model was constructed based on the 2.3-Å-resolution x-ray crystallographic structure of active-site inhibited human FXa (PDB:1XKA). The missing ␥-carboxyglutamic acid (GLA) and part of epidermal growth factor 1 (EGF1) domains of the light chain were modeled based on the template of GLA-EGF1 domains of the tissue factor (TF)-bound FVIIa structure (PDB:1DAN). The activation peptide and other missing segments of FX were introduced using homology modeling. The full calcium-bound model of FX was subjected to 6.2 ns of molecular dynamics simulation in aqueous medium using the AMBER6.0 package. We observed significant reorientation of the serine-protease (SP) domain upon activation leading to a compact multi-domain structure. The solution structure of zymogen appears to be in a well-extended conformation with the distance between the calcium ions in the GLA domain and the catalytic residues estimated to be ϳ95 Å in contrast to ϳ83 Å in the activated form. The latter is in close agreement with fluorescence studies on FXa. The S1-specificity residues near the catalytic triad show significant differences between the zymogen and activated structures.
... Coray M. Colina 1 , Robert E. Duke 2 , Divi Venkateswarlu 3 , Lalith Perera 2 , Tom Darden 2 ... more ... Coray M. Colina 1 , Robert E. Duke 2 , Divi Venkateswarlu 3 , Lalith Perera 2 , Tom Darden 2 , and Lee G Pedersen 1 . (1) Department of Chemistry ... We performed systematic MD simulations of this complex, using the AMBER suite, for over 22 ns each at different conditions. ...