From Gene to Drug: A Proof of Concept for a Plausible Computational Pathway

Shenoy, Sandhya R.; Jayaram, B.; Latha, N.; Narang, Pooja; Jain, Tarun; Bhushan, Kumkum; Shaikh, Saher A.; Bose, Surojit; Sharma, Pankaj; Singhal, Poonam; Gandhimathi, A.; Agrawal, Praveen; Pandey, Vidhu; Dutta, Samrat; Sandhu, Gurvisha; Gupta, Anuj; Shekhar, Shashank; Tripathi, Shailesh

doi:10.1109/isda.2006.154

Cited by 3 publications

(5 citation statements)

References 13 publications

(11 reference statements)

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“…With rapid advances in the area, there is a growing need to develop efficient versatile bioinformatics software packages which are hypotheses driven. 'Gene to Drug' developed at SCFBio, IIT Delhi is an attempt in this pursuit and an integration of heterologous applications of different technologies developed in-house and their translation into in silico products that cater to a majority of bioinformatics applications and how grid services and high performance computing platforms can be harnessed to bridge the gap between biomolecular sequence, structure and function [243].…”

Section: Discussionmentioning

confidence: 99%

Proteins: Sequence to Structure and Function – Current Status

Shenoy

Jayaram²

2010

CPPS

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In an era that has been dominated by Structural Biology for the last 30-40 years, a dramatic change of focus towards sequence analysis has spurred the advent of the genome projects and the resultant diverging sequence/structure deficit. The central challenge of Computational Structural Biology is therefore to rationalize the mass of sequence information into biochemical and biophysical knowledge and to decipher the structural, functional and evolutionary clues encoded in the language of biological sequences. In investigating the meaning of sequences, two distinct analytical themes have emerged: in the first approach, pattern recognition techniques are used to detect similarity between sequences and hence to infer related structures and functions; in the second ab initio prediction methods are used to deduce 3D structure, and ultimately to infer function, directly from the linear sequence. In this article, we attempt to provide a critical assessment of what one may and may not expect from the biological sequences and to identify major issues yet to be resolved. The presentation is organized under several subtitles like protein sequences, pattern recognition techniques, protein tertiary structure prediction, membrane protein bioinformatics, human proteome, protein-protein interactions, metabolic networks, potential drug targets based on simple sequence properties, disordered proteins, the sequence-structure relationship and chemical logic of protein sequences.

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Section: Discussionmentioning

confidence: 99%

Proteins: Sequence to Structure and Function – Current Status

Shenoy

Jayaram²

2010

CPPS

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“…Guanine–cytosine (G–C) and adenine–thymine (A–T) positions were based on the standard double-stranded B-DNA form in the (5′ → 3′) CAACTAGCCGGT sequence. 49 , 50 The sugar-phosphate backbone was protonated in order to obtain a neutral structure as recommended for mimicking these fragments with DFT methods. 51 , 52 …”

Section: Models and Methodsmentioning

confidence: 99%

“…A larger DNA model (type 3) was next designed with a complete two-base-pair fragment, which also includes the lateral sugar-phosphate backbone. Guanine–cytosine (G–C) and adenine–thymine (A–T) positions were based on the standard double-stranded B-DNA form in the (5′ → 3′) CAACTAGCCGGT sequence. , The sugar-phosphate backbone was protonated in order to obtain a neutral structure as recommended for mimicking these fragments with DFT methods. , …”

Section: Models and Methodsmentioning

confidence: 99%

“…Guanine−cytosine (G−C) and adenine−thymine (A−T) positions were based on the standard double-stranded B-DNA form in the (5′ → 3′) CAACTAGCCGGT sequence. 49,50 The sugar-phosphate backbone was protonated in order to obtain a neutral structure as recommended for mimicking these fragments with DFT methods. 51,52 Similar DNA models were used for the chloro and aqua complexes with a single base interacting with different sides of the phenanthridine plane (types 4 and 5, bottom panel in Figure 1).…”

Section: ■ Introductionmentioning

confidence: 99%

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Intercalation Ability of Novel Monofunctional Platinum Anticancer Drugs: A Key Step in Their Biological Action

Veclani

Tolazzi

Cerón‐Carrasco

et al. 2021

J. Chem. Inf. Model.

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Phenanthriplatin (PtPPH) is a monovalent platinum(II)-based complex with a large cytotoxicity against cancer cells. Although the aqua-activated drug has been assumed to be the precursor for DNA damage, it is still under debate whether the way in which that metallodrug attacks to DNA is dominated by a direct binding to a guanine base or rather by an intercalated intermediate product. Aiming to capture the mechanism of action of PtPPH, the present contribution used theoretical tools to systematically assess the sequence of all possible mechanisms on drug activation and reactivity, for example, hydrolysis, intercalation, and covalent damage to DNA. Ab initio quantum mechanical (QM) methods, hybrid QM/QM′ schemes, and independent gradient model approaches are implemented in an unbiased protocol. The performed simulations show that the cascade of reactions is articulated in three well-defined stages: (i) an early and fast intercalation of the complex between the DNA bases, (ii) a subsequent hydrolysis reaction that leads to the aqua-activated form, and (iii) a final formation of the covalent bond between PtPPH and DNA at a guanine site. The permanent damage to DNA is consequently driven by that latter bond to DNA but with a simultaneous π–π intercalation of the phenanthridine into nucleobases. The impact of the DNA sequence and the lateral backbone was also discussed to provide a more complete picture of the forces that anchor the drug into the double helix.

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“…Desta forma, métodos e componentes de interface são tipicamente baseados no paradigma Windows-Icon-Mouse-Pointer (WIMP), amplamente utilizados em PCs, permitindo o uso de várias janelas de trabalho simultâneas (McFaddin & Rice, 1992) e funcionalidades do tipo drag-and-drop (Manjunatha et al, 2011). Uma lista não-exaustiva de componentes típicos inclui: barras de ferramente; mapas; menus drop-down; caixas de seleção (Rocha et al, 2001); menus; barras de status; sequenciadores numéricos (numerical steppers) (Lundstrom & Klimeck, 2006); paletas de ferramentas (Takatsuka & Gahegan, 2001); botões de rádio (radio buttons); janelas de diálogo; janelas de texto; menus não-persistentes; seções sanfona (expandable stacks) (Fine et al, 1998); planilhas (Willson et al, 1992); formulários (Shenoy et al, 2006); abas (Caroli et al, 2004);…”

Section: Quanto àS Plataformas De Uso E Desenvolvimentounclassified

A Ciência Como Jogo: Abordagens Lúdicas Ao Design De Interfaces Para Software Científico

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From Gene to Drug: A Proof of Concept for a Plausible Computational Pathway

Abstract: Abstract

Cited by 3 publications

References 13 publications

Proteins: Sequence to Structure and Function – Current Status

Proteins: Sequence to Structure and Function – Current Status

Intercalation Ability of Novel Monofunctional Platinum Anticancer Drugs: A Key Step in Their Biological Action

A Ciência Como Jogo: Abordagens Lúdicas Ao Design De Interfaces Para Software Científico

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