The Power of Molecular Dynamics Simulations and Their Applications to Discover Cysteine Protease Inhibitors
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
A large family of enzymes with the function of hydrolyzing peptide bonds, called peptidases or cysteine proteases (CPs), are divided into three categories according to the peptide chain involved. CPs catalyze the hydrolysis of amide, ester, thiol ester, and thioester peptide bonds. They can be divided into several groups, such as papain-like (CA), viral chymotrypsin-like CPs (CB), papain-like endopeptidases of RNA viruses (CC), legumain-type caspases (CD), and showing active residues of His, Glu/Asp, Gln, Cys (CE). The catalytic mechanism of CPs is the essential cysteine residue present in the active site. These mechanisms are often studied through computational methods that provide new information about the catalytic mechanism and identify inhibitors. The role of computational methods during drug design and development stages is increasing. Methods in Computer-Aided Drug Design (CADD) accelerate the discovery process, increase the chances of selecting more promising molecules for experimental studies, and can identify critical mechanisms involved in the pathophysiology and molecular pathways of action. Molecular dynamics (MD) simulations are essential in any drug discovery program due to their high capacity for simulating a physiological environment capable of unveiling significant inhibition mechanisms of new compounds against target proteins, especially CPs. Here, a brief approach will be shown on MD simulations and how the studies were applied to identify inhibitors or critical information against cysteine protease from several microorganisms, such as Trypanosoma cruzi (cruzain), Trypanosoma brucei (rhodesain), Plasmodium spp. (falcipain), and SARS-CoV-2 (Mpro). We hope the readers will gain new insights and use our study as a guide for potential compound identifications using MD simulations.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
|---|---|
| Enthalten in: |
Mini reviews in medicinal chemistry - (2023) vom: 01. Sept. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Dos Santos Nascimento, Igor José [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Computational Chemistry |
|---|
| Anmerkungen: |
Date Revised 08.09.2023 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.2174/1389557523666230901152257 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM361777248 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM361777248 | ||
| 003 | DE-627 | ||
| 005 | 20231226085844.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.2174/1389557523666230901152257 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1205.xml |
| 035 | |a (DE-627)NLM361777248 | ||
| 035 | |a (NLM)37680157 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Dos Santos Nascimento, Igor José |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Power of Molecular Dynamics Simulations and Their Applications to Discover Cysteine Protease Inhibitors |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 08.09.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a A large family of enzymes with the function of hydrolyzing peptide bonds, called peptidases or cysteine proteases (CPs), are divided into three categories according to the peptide chain involved. CPs catalyze the hydrolysis of amide, ester, thiol ester, and thioester peptide bonds. They can be divided into several groups, such as papain-like (CA), viral chymotrypsin-like CPs (CB), papain-like endopeptidases of RNA viruses (CC), legumain-type caspases (CD), and showing active residues of His, Glu/Asp, Gln, Cys (CE). The catalytic mechanism of CPs is the essential cysteine residue present in the active site. These mechanisms are often studied through computational methods that provide new information about the catalytic mechanism and identify inhibitors. The role of computational methods during drug design and development stages is increasing. Methods in Computer-Aided Drug Design (CADD) accelerate the discovery process, increase the chances of selecting more promising molecules for experimental studies, and can identify critical mechanisms involved in the pathophysiology and molecular pathways of action. Molecular dynamics (MD) simulations are essential in any drug discovery program due to their high capacity for simulating a physiological environment capable of unveiling significant inhibition mechanisms of new compounds against target proteins, especially CPs. Here, a brief approach will be shown on MD simulations and how the studies were applied to identify inhibitors or critical information against cysteine protease from several microorganisms, such as Trypanosoma cruzi (cruzain), Trypanosoma brucei (rhodesain), Plasmodium spp. (falcipain), and SARS-CoV-2 (Mpro). We hope the readers will gain new insights and use our study as a guide for potential compound identifications using MD simulations | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Computational Chemistry | |
| 650 | 4 | |a Computer-Aided Drug Design | |
| 650 | 4 | |a Cysteine Protease | |
| 650 | 4 | |a Molecular Mechanics | |
| 650 | 4 | |a Molecular Modeling | |
| 650 | 4 | |a Neglected Tropical Diseases | |
| 700 | 1 | |a Santana Gomes, Joilly Nilce |e verfasserin |4 aut | |
| 700 | 1 | |a de Oliveira Viana, Jéssika |e verfasserin |4 aut | |
| 700 | 1 | |a de Medeiros E Silva, Yvnni Maria Sales |e verfasserin |4 aut | |
| 700 | 1 | |a Barbosa, Euzébio Guimarães |e verfasserin |4 aut | |
| 700 | 1 | |a de Moura, Ricardo Olimpio |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Mini reviews in medicinal chemistry |d 2001 |g (2023) vom: 01. Sept. |w (DE-627)NLM121595404 |x 1875-5607 |7 nnns |
| 773 | 1 | 8 | |g year:2023 |g day:01 |g month:09 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.2174/1389557523666230901152257 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2023 |b 01 |c 09 | ||