Nuria Centeno | Pompeu Fabra University (original) (raw)
Papers by Nuria Centeno
Molecular Modeling and Prediction of Bioactivity, 2000
Heterocyclic aromatic amines (HCA) present in cooked food, exert a genotoxic activity after metab... more Heterocyclic aromatic amines (HCA) present in cooked food, exert a genotoxic activity after metabolism (N-oxidation) by cytochrome P450 1A21. Two different 3D-QSAR approaches (COMBINE2 and GRID/GOLPE3) have been applied to a series of 12 HCAs showing different degrees of mutagenic activity (Figure 1).
Biochemistry and Molecular Biology Education, 2003
Understanding the basic principles of structural biology is becoming a major subject of study in ... more Understanding the basic principles of structural biology is becoming a major subject of study in most undergraduate level programs in biology. In the genomic and proteomic age, it is becoming indispensable for biology students to master concepts related to the sequence and structure of proteins in order to develop skills that may be useful in a wide range of applications. Within this context, this article shows a scheme for teaching structural biology based on hands-on computer approaches, including computational genomics, and structural bioinformatics tools. The students learn to use most of the leading computer programs available for the complete path that goes from sequence to structure and eventually function. During the course, they are taught to build models of proteins based on sequence and structure information. The students are also provided with a critical point of view on automatic procedures and learn to discern between likely and unlikely structures of their final models.
Bioorganic & Medicinal Chemistry, 2020
Journal of Medicinal Chemistry, Jan 12, 2006
Over two hundred 1-, 3-, 8-, and 9-substituted-9-deazaxanthines were prepared and evaluated for t... more Over two hundred 1-, 3-, 8-, and 9-substituted-9-deazaxanthines were prepared and evaluated for their binding affinity at the recombinant human adenosine receptors, in particular at the hA 2B and hA 2A subtypes. Several ligands endowed with sub-micromolar to low nanomolar binding affinity at hA 2B receptors, good selectivity over hA 2A and hA 3 , but a relatively poor selectivity over hA 1 were obtained. Good antagonistic potencies and efficacies, with pA 2 values close to the corresponding pK i s, were observed in functional assays in vitro performed on a selected series of compounds. 1,3-Dimethyl-8-phenoxy-(N-p-halogenophenyl)-acetamido-9-deazaxanthine derivatives appeared as the most interesting leads, some of them showing outstanding hA 2B affinities, high selectivity over hA 2A and hA 3 , but low selectivity over hA 1. Structure-affinity relationships suggested that the binding potency at the hA 2B receptor was mainly modulated by the steric (lipophilic) properties of the substituents at positions 1 and 3 and by the electronic and lipophilic characteristics of the substituents at position 8. A comparison among affinity and selectivity profiles of 9-deazaxanthines with the corresponding xanthines suggested some possible differences in their binding mode.
Acta Crystallographica Section A Foundations of Crystallography, 2011
PLoS ONE, 2009
The thyroid hormone and retinol transporter protein known as transthyretin (TTR) is in the origin... more The thyroid hormone and retinol transporter protein known as transthyretin (TTR) is in the origin of one of the 20 or so known amyloid diseases. TTR self assembles as a homotetramer leaving a central hydrophobic channel with two symmetrical binding sites. The aggregation pathway of TTR into amiloid fibrils is not yet well characterized but in vitro binding of thyroid hormones and other small organic molecules to TTR binding channel results in tetramer stabilization which prevents amyloid formation in an extent which is proportional to the binding constant. Up to now, TTR aggregation inhibitors have been designed looking at various structural features of this binding channel others than its ability to host iodine atoms. In the present work, greatly improved inhibitors have been designed and tested by taking into account that thyroid hormones are unique in human biochemistry owing to the presence of multiple iodine atoms in their molecules which are probed to interact with specific halogen binding domains sitting at the TTR binding channel. The new TTR fibrillogenesis inhibitors are based on the diflunisal core structure because diflunisal is a registered salicylate drug with NSAID activity now undergoing clinical trials for TTR amyloid diseases. Biochemical and biophysical evidence confirms that iodine atoms can be an important design feature in the search for candidate drugs for TTR related amyloidosis.
Journal of Peptide Science, 1997
The conformational preferences of peptide T (ASTTTNYT) were analysed by means of computational me... more The conformational preferences of peptide T (ASTTTNYT) were analysed by means of computational methods. A thorough exploration of the conformational space was carried out within the framework of the molecular mechanics approach, using simulated annealing as a searching strategy. Specifically, in order to obtain a subset of low-energy conformations with energies close to the global minimum as complete as possible, a simulated annealing protocol was repeated several times in a recursive fashion. The results of the search indicate that the peptide exhibits a a-helical character although most of the conformations characterized, including the global minimum, can be described as bent conformations. Conformations exhibiting b-turn motives previously proposed from NMR studies were also characterized, although they are not very predominant in the set of low-energy conformations.
Journal of Biomolecular Structure and Dynamics, 1998
The AMBER 4.0 force field was used to perform the characterization of the conformational profile ... more The AMBER 4.0 force field was used to perform the characterization of the conformational profile of the highly potent bradykinin antagonist Hoe-140 (D-Arg0-Arg1-Pro2-Hyp3-Gly4-Thi5-Ser6-D-++ +Tic7-Oic8-Arg9). The structural features of the peptide were assessed using two different computational methods, both capable to provide a good sampling of the low-energy conformations of the molecule. Specifically, the conformational space of the peptide was explored: i) computing molecular dynamics trajectories in cycles of high (900 K) and low (300 K) temperature and ii) using simulated annealing (SA) in an iterative fashion. Analysis of the structures characterized indicates that most of the low-energy conformations of the peptide exhibit a betaII&amp;#39;-turn motif at its C-terminus, in agreement with previous experimental and theoretical studies. On the other hand, about a 50% of the low-energy conformations characterized also exhibit different beta-turn type motifs at the N-terminus, whereas the rest of the conformations can be described as bends. Finally, in order to get new insights into the structural requirements necessary to design more potent and selective antagonists of bradykinin, present results were compared with those previously reported by this laboratory on the conformational preferences of the native nonapeptide and its DPhe7 analog.
The Journal of Peptide Research, 2009
A conformational analysis of the fragment 110-121 of VP3 coating protein of the hepatitis A virus... more A conformational analysis of the fragment 110-121 of VP3 coating protein of the hepatitis A virus was carried out using circular dichroism spectroscopy and computational studies. The latter studies indicate the tendency of the peptide to adopt hairpin-type structures. Circular dichroism experiments indicate that, in spite of the fact that the isolated peptide exhibits no structure under different experimental conditions, negatively charged liposomes induce a secondary structure that agrees with the results of the computational study.
Biochemistry and Molecular Biology Education, 2003
Abstract Understanding the basic principles of structural biology is becoming a major subject of ... more Abstract Understanding the basic principles of structural biology is becoming a major subject of study in most undergraduate level programs in biology. In the genomic and proteomic age, it is becoming indispensable for biology students to master concepts related to the sequence and structure of proteins in order to develop skills that may be useful in a wide range of applications. Within this context, this article shows a scheme for teaching structural biology based on hands-on computer approaches, including computational genomics, ...
Chemical Physics Letters, 1995
The distribution of minima of thorough conformational searches of the pentapeptide met-enkephalin... more The distribution of minima of thorough conformational searches of the pentapeptide met-enkephalin and the nonapeptide bradykinin was compared with the density of states of a flexible molecule described using the rotational isomeric approximation. It is observed that minima distributions generated from the conformational search and the density of states of the rotational isomeric model exhibit the same feature: an asymmetric distribution with a maximum. This result together with the energy landscape of a polypeptide provides new insights into the multiple minima problem. The implications on devising more robust conformational search strategies are discussed.
Proteins Structure Function and Bioinformatics, Mar 1, 2004
The present work describes the building of a human A 1 adenosine receptor (hA 1 AR) model, based ... more The present work describes the building of a human A 1 adenosine receptor (hA 1 AR) model, based on the X-ray crystal structure of bovine rhodopsin, and its use as a basis for the investigation of some important structural characteristics of the receptor. One of the issues investigated was the protonation position of two histidine residues known to influence ligand binding, with protonation of His251 (6.52) in epsilon position and His278 (7.43) in delta position showing the best agreement with experimental evidence. The model was also used to study the position and structural role of water molecules present in the helical bundle. Finally, the binding site location and the ligand docking were investigated using an objective strategy. A suitable site for the binding of the ribose moiety of adenosine was first postulated and further confirmed by means of a novel chemometric strategy based on GRIND descriptors. Using this position as an anchor point, the binding of adenosine was studied by docking and molecular dynamics simulations obtaining two putative binding positions in good agreement with experimental data. Proteins 2004; 54:705-715.
Journal of Molecular Structure: THEOCHEM, 1996
Minima distribution of thorough conformational searches of three peptides of different length ran... more Minima distribution of thorough conformational searches of three peptides of different length ranging from five to nine residues, were compared with the density of states of a flexible molecule derived from the rotational isomeric approximation. It is observed that minima distributions generated from the conformational searches exhibit the same characteristics as the density of states derived from the rotational isomeric model: an asymmetric distribution with a maximum. These results together with a more profound understanding of the characteristics of the energy landscapes of polypeptides, provide new insights into the multiple minima problem. The implications in devising more robust conformational search strategies are discussed.
Journal of Biomolecular Structure Dynamics, Nov 1, 1996
In order to investigate the relationship between the bioactive conformation of a peptide and its ... more In order to investigate the relationship between the bioactive conformation of a peptide and its set of thermodynamically accessible structures in solution, the conformational profile of the tetrapeptide Ac-Pro-Ala-Pro-Tyr-OH was characterized by computational methods. Search of the conformational space was performed within the molecular mechanics frame-work using the AMBER4.0 force field with an effective dielectric constant of 80. Unique structures of the peptide were compared with its bioactive conformation for the protein Streptomyces griseus Protease A, as taken from the crystal structure of the enzyme-peptide complex. The results show that the bound conformation is close to one of the unique conformations characterized in the conformational search of the isolated peptide. Moreover, the lowest energy minimum characterized in the conformational search exhibits large deviations when compared to the bound conformation of the crystal structure.
Biochemistry and Molecular Biology Education, 2003
Understanding the basic principles of structural biology is becoming a major subject of study in ... more Understanding the basic principles of structural biology is becoming a major subject of study in most undergraduate level programs in biology. In the genomic and proteomic age, it is becoming indispensable for biology students to master concepts related to the sequence and structure of proteins in order to develop skills that may be useful in a wide range of applications. Within this context, this article shows a scheme for teaching structural biology based on hands-on computer approaches, including computational genomics, and structural bioinformatics tools. The students learn to use most of the leading computer programs available for the complete path that goes from sequence to structure and eventually function. During the course, they are taught to build models of proteins based on sequence and structure information. The students are also provided with a critical point of view on automatic procedures and learn to discern between likely and unlikely structures of their final models.
![Research paper thumbnail of Corrigendum to “1-, 3- and 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A 2B adenosine receptor” [Bioorg. Med. Chem. 16 (2008) 2852–2869]](https://attachments.academia-assets.com/41322372/thumbnails/1.jpg)
](Bioorgan Med Chem, 2008
Corrigendum to ''1-, 3-and 8-substituted-9-deazaxanthines as potent and selective antagonists at ... more Corrigendum to ''1-, 3-and 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A 2B adenosine receptor"
Microbial cell factories, Jan 30, 2005
Comparative modeling is becoming an increasingly helpful technique in microbial cell factories as... more Comparative modeling is becoming an increasingly helpful technique in microbial cell factories as the knowledge of the three-dimensional structure of a protein would be an invaluable aid to solve problems on protein production. For this reason, an introduction to comparative modeling is presented, with special emphasis on the basic concepts, opportunities and challenges of protein structure prediction. This review is intended to serve as a guide for the biologist who has no special expertise and who is not involved in the determination of protein structure. Selected applications of comparative modeling in microbial cell factories are outlined, and the role of microbial cell factories in the structural genomics initiative is discussed.
Journal of computer-aided molecular design, 1997
The three-dimensional modelling of proteins is a useful tool to fill the gap between the number o... more The three-dimensional modelling of proteins is a useful tool to fill the gap between the number of sequenced proteins and the number of experimentally known 3D structures. However, when the degree of homology between the protein and the available 3D templates is low, model building becomes a difficult task and the reliability of the results depends critically on the correctness of the sequence alignment. For this reason, we have undertaken the modelling of human cytochrome P450 1A2 starting by a careful analysis of several sequence alignment strategies (multiple sequence alignments and the TOPITS threading technique). The best results were obtained using TOPITS followed by a manual refinement to avoid unlikely gaps. Because TOPITS uses secondary structure predictions, several methods that are available for this purpose (Levin, Gibrat, DPM, NnPredict, PHD, SOPM and NNSP) have also been evaluated on cytochromes P450 with known 3D structures. More reliable predictions on alpha-helices ...
The authors regret that the Catalyst/Hiphop outcome has been erroneously reported, though this do... more The authors regret that the Catalyst/Hiphop outcome has been erroneously reported, though this does not involve any change in the discussion of results and conclusions. On p. 867 Figure 5 is incorrect, the correct figure is given below: includegraphics10347f1.eps includegraphics10347f1b.eps
Molecular Modeling and Prediction of Bioactivity, 2000
Heterocyclic aromatic amines (HCA) present in cooked food, exert a genotoxic activity after metab... more Heterocyclic aromatic amines (HCA) present in cooked food, exert a genotoxic activity after metabolism (N-oxidation) by cytochrome P450 1A21. Two different 3D-QSAR approaches (COMBINE2 and GRID/GOLPE3) have been applied to a series of 12 HCAs showing different degrees of mutagenic activity (Figure 1).
Biochemistry and Molecular Biology Education, 2003
Understanding the basic principles of structural biology is becoming a major subject of study in ... more Understanding the basic principles of structural biology is becoming a major subject of study in most undergraduate level programs in biology. In the genomic and proteomic age, it is becoming indispensable for biology students to master concepts related to the sequence and structure of proteins in order to develop skills that may be useful in a wide range of applications. Within this context, this article shows a scheme for teaching structural biology based on hands-on computer approaches, including computational genomics, and structural bioinformatics tools. The students learn to use most of the leading computer programs available for the complete path that goes from sequence to structure and eventually function. During the course, they are taught to build models of proteins based on sequence and structure information. The students are also provided with a critical point of view on automatic procedures and learn to discern between likely and unlikely structures of their final models.
Bioorganic & Medicinal Chemistry, 2020
Journal of Medicinal Chemistry, Jan 12, 2006
Over two hundred 1-, 3-, 8-, and 9-substituted-9-deazaxanthines were prepared and evaluated for t... more Over two hundred 1-, 3-, 8-, and 9-substituted-9-deazaxanthines were prepared and evaluated for their binding affinity at the recombinant human adenosine receptors, in particular at the hA 2B and hA 2A subtypes. Several ligands endowed with sub-micromolar to low nanomolar binding affinity at hA 2B receptors, good selectivity over hA 2A and hA 3 , but a relatively poor selectivity over hA 1 were obtained. Good antagonistic potencies and efficacies, with pA 2 values close to the corresponding pK i s, were observed in functional assays in vitro performed on a selected series of compounds. 1,3-Dimethyl-8-phenoxy-(N-p-halogenophenyl)-acetamido-9-deazaxanthine derivatives appeared as the most interesting leads, some of them showing outstanding hA 2B affinities, high selectivity over hA 2A and hA 3 , but low selectivity over hA 1. Structure-affinity relationships suggested that the binding potency at the hA 2B receptor was mainly modulated by the steric (lipophilic) properties of the substituents at positions 1 and 3 and by the electronic and lipophilic characteristics of the substituents at position 8. A comparison among affinity and selectivity profiles of 9-deazaxanthines with the corresponding xanthines suggested some possible differences in their binding mode.
Acta Crystallographica Section A Foundations of Crystallography, 2011
PLoS ONE, 2009
The thyroid hormone and retinol transporter protein known as transthyretin (TTR) is in the origin... more The thyroid hormone and retinol transporter protein known as transthyretin (TTR) is in the origin of one of the 20 or so known amyloid diseases. TTR self assembles as a homotetramer leaving a central hydrophobic channel with two symmetrical binding sites. The aggregation pathway of TTR into amiloid fibrils is not yet well characterized but in vitro binding of thyroid hormones and other small organic molecules to TTR binding channel results in tetramer stabilization which prevents amyloid formation in an extent which is proportional to the binding constant. Up to now, TTR aggregation inhibitors have been designed looking at various structural features of this binding channel others than its ability to host iodine atoms. In the present work, greatly improved inhibitors have been designed and tested by taking into account that thyroid hormones are unique in human biochemistry owing to the presence of multiple iodine atoms in their molecules which are probed to interact with specific halogen binding domains sitting at the TTR binding channel. The new TTR fibrillogenesis inhibitors are based on the diflunisal core structure because diflunisal is a registered salicylate drug with NSAID activity now undergoing clinical trials for TTR amyloid diseases. Biochemical and biophysical evidence confirms that iodine atoms can be an important design feature in the search for candidate drugs for TTR related amyloidosis.
Journal of Peptide Science, 1997
The conformational preferences of peptide T (ASTTTNYT) were analysed by means of computational me... more The conformational preferences of peptide T (ASTTTNYT) were analysed by means of computational methods. A thorough exploration of the conformational space was carried out within the framework of the molecular mechanics approach, using simulated annealing as a searching strategy. Specifically, in order to obtain a subset of low-energy conformations with energies close to the global minimum as complete as possible, a simulated annealing protocol was repeated several times in a recursive fashion. The results of the search indicate that the peptide exhibits a a-helical character although most of the conformations characterized, including the global minimum, can be described as bent conformations. Conformations exhibiting b-turn motives previously proposed from NMR studies were also characterized, although they are not very predominant in the set of low-energy conformations.
Journal of Biomolecular Structure and Dynamics, 1998
The AMBER 4.0 force field was used to perform the characterization of the conformational profile ... more The AMBER 4.0 force field was used to perform the characterization of the conformational profile of the highly potent bradykinin antagonist Hoe-140 (D-Arg0-Arg1-Pro2-Hyp3-Gly4-Thi5-Ser6-D-++ +Tic7-Oic8-Arg9). The structural features of the peptide were assessed using two different computational methods, both capable to provide a good sampling of the low-energy conformations of the molecule. Specifically, the conformational space of the peptide was explored: i) computing molecular dynamics trajectories in cycles of high (900 K) and low (300 K) temperature and ii) using simulated annealing (SA) in an iterative fashion. Analysis of the structures characterized indicates that most of the low-energy conformations of the peptide exhibit a betaII&amp;#39;-turn motif at its C-terminus, in agreement with previous experimental and theoretical studies. On the other hand, about a 50% of the low-energy conformations characterized also exhibit different beta-turn type motifs at the N-terminus, whereas the rest of the conformations can be described as bends. Finally, in order to get new insights into the structural requirements necessary to design more potent and selective antagonists of bradykinin, present results were compared with those previously reported by this laboratory on the conformational preferences of the native nonapeptide and its DPhe7 analog.
The Journal of Peptide Research, 2009
A conformational analysis of the fragment 110-121 of VP3 coating protein of the hepatitis A virus... more A conformational analysis of the fragment 110-121 of VP3 coating protein of the hepatitis A virus was carried out using circular dichroism spectroscopy and computational studies. The latter studies indicate the tendency of the peptide to adopt hairpin-type structures. Circular dichroism experiments indicate that, in spite of the fact that the isolated peptide exhibits no structure under different experimental conditions, negatively charged liposomes induce a secondary structure that agrees with the results of the computational study.
Biochemistry and Molecular Biology Education, 2003
Abstract Understanding the basic principles of structural biology is becoming a major subject of ... more Abstract Understanding the basic principles of structural biology is becoming a major subject of study in most undergraduate level programs in biology. In the genomic and proteomic age, it is becoming indispensable for biology students to master concepts related to the sequence and structure of proteins in order to develop skills that may be useful in a wide range of applications. Within this context, this article shows a scheme for teaching structural biology based on hands-on computer approaches, including computational genomics, ...
Chemical Physics Letters, 1995
The distribution of minima of thorough conformational searches of the pentapeptide met-enkephalin... more The distribution of minima of thorough conformational searches of the pentapeptide met-enkephalin and the nonapeptide bradykinin was compared with the density of states of a flexible molecule described using the rotational isomeric approximation. It is observed that minima distributions generated from the conformational search and the density of states of the rotational isomeric model exhibit the same feature: an asymmetric distribution with a maximum. This result together with the energy landscape of a polypeptide provides new insights into the multiple minima problem. The implications on devising more robust conformational search strategies are discussed.
Proteins Structure Function and Bioinformatics, Mar 1, 2004
The present work describes the building of a human A 1 adenosine receptor (hA 1 AR) model, based ... more The present work describes the building of a human A 1 adenosine receptor (hA 1 AR) model, based on the X-ray crystal structure of bovine rhodopsin, and its use as a basis for the investigation of some important structural characteristics of the receptor. One of the issues investigated was the protonation position of two histidine residues known to influence ligand binding, with protonation of His251 (6.52) in epsilon position and His278 (7.43) in delta position showing the best agreement with experimental evidence. The model was also used to study the position and structural role of water molecules present in the helical bundle. Finally, the binding site location and the ligand docking were investigated using an objective strategy. A suitable site for the binding of the ribose moiety of adenosine was first postulated and further confirmed by means of a novel chemometric strategy based on GRIND descriptors. Using this position as an anchor point, the binding of adenosine was studied by docking and molecular dynamics simulations obtaining two putative binding positions in good agreement with experimental data. Proteins 2004; 54:705-715.
Journal of Molecular Structure: THEOCHEM, 1996
Minima distribution of thorough conformational searches of three peptides of different length ran... more Minima distribution of thorough conformational searches of three peptides of different length ranging from five to nine residues, were compared with the density of states of a flexible molecule derived from the rotational isomeric approximation. It is observed that minima distributions generated from the conformational searches exhibit the same characteristics as the density of states derived from the rotational isomeric model: an asymmetric distribution with a maximum. These results together with a more profound understanding of the characteristics of the energy landscapes of polypeptides, provide new insights into the multiple minima problem. The implications in devising more robust conformational search strategies are discussed.
Journal of Biomolecular Structure Dynamics, Nov 1, 1996
In order to investigate the relationship between the bioactive conformation of a peptide and its ... more In order to investigate the relationship between the bioactive conformation of a peptide and its set of thermodynamically accessible structures in solution, the conformational profile of the tetrapeptide Ac-Pro-Ala-Pro-Tyr-OH was characterized by computational methods. Search of the conformational space was performed within the molecular mechanics frame-work using the AMBER4.0 force field with an effective dielectric constant of 80. Unique structures of the peptide were compared with its bioactive conformation for the protein Streptomyces griseus Protease A, as taken from the crystal structure of the enzyme-peptide complex. The results show that the bound conformation is close to one of the unique conformations characterized in the conformational search of the isolated peptide. Moreover, the lowest energy minimum characterized in the conformational search exhibits large deviations when compared to the bound conformation of the crystal structure.
Biochemistry and Molecular Biology Education, 2003
Understanding the basic principles of structural biology is becoming a major subject of study in ... more Understanding the basic principles of structural biology is becoming a major subject of study in most undergraduate level programs in biology. In the genomic and proteomic age, it is becoming indispensable for biology students to master concepts related to the sequence and structure of proteins in order to develop skills that may be useful in a wide range of applications. Within this context, this article shows a scheme for teaching structural biology based on hands-on computer approaches, including computational genomics, and structural bioinformatics tools. The students learn to use most of the leading computer programs available for the complete path that goes from sequence to structure and eventually function. During the course, they are taught to build models of proteins based on sequence and structure information. The students are also provided with a critical point of view on automatic procedures and learn to discern between likely and unlikely structures of their final models.
Bioorgan Med Chem, 2008
Corrigendum to ''1-, 3-and 8-substituted-9-deazaxanthines as potent and selective antagonists at ... more Corrigendum to ''1-, 3-and 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A 2B adenosine receptor"
Microbial cell factories, Jan 30, 2005
Comparative modeling is becoming an increasingly helpful technique in microbial cell factories as... more Comparative modeling is becoming an increasingly helpful technique in microbial cell factories as the knowledge of the three-dimensional structure of a protein would be an invaluable aid to solve problems on protein production. For this reason, an introduction to comparative modeling is presented, with special emphasis on the basic concepts, opportunities and challenges of protein structure prediction. This review is intended to serve as a guide for the biologist who has no special expertise and who is not involved in the determination of protein structure. Selected applications of comparative modeling in microbial cell factories are outlined, and the role of microbial cell factories in the structural genomics initiative is discussed.
Journal of computer-aided molecular design, 1997
The three-dimensional modelling of proteins is a useful tool to fill the gap between the number o... more The three-dimensional modelling of proteins is a useful tool to fill the gap between the number of sequenced proteins and the number of experimentally known 3D structures. However, when the degree of homology between the protein and the available 3D templates is low, model building becomes a difficult task and the reliability of the results depends critically on the correctness of the sequence alignment. For this reason, we have undertaken the modelling of human cytochrome P450 1A2 starting by a careful analysis of several sequence alignment strategies (multiple sequence alignments and the TOPITS threading technique). The best results were obtained using TOPITS followed by a manual refinement to avoid unlikely gaps. Because TOPITS uses secondary structure predictions, several methods that are available for this purpose (Levin, Gibrat, DPM, NnPredict, PHD, SOPM and NNSP) have also been evaluated on cytochromes P450 with known 3D structures. More reliable predictions on alpha-helices ...
The authors regret that the Catalyst/Hiphop outcome has been erroneously reported, though this do... more The authors regret that the Catalyst/Hiphop outcome has been erroneously reported, though this does not involve any change in the discussion of results and conclusions. On p. 867 Figure 5 is incorrect, the correct figure is given below: includegraphics10347f1.eps includegraphics10347f1b.eps