TY - JOUR

T1 - Methods and Applications of In Silico Aptamer Design and Modeling

AU - Буглак, Андрей Андреевич

AU - Самохвалов, Алексей

AU - Жердев, Анатолий

AU - Дзантиев, Борис

N1 - Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2020/11/2

Y1 - 2020/11/2

N2 - Aptamers are nucleic acid analogues of antibodies with high affinity to different targets, such as cells, viruses, proteins, inorganic materials, and coenzymes. Empirical approaches allow the design of in vitro aptamers that bind particularly to a target molecule with high affinity and selectivity. Theoretical methods allow significant expansion of the possibilities of aptamer design. In this study, we review theoretical and joint theoretical-experimental studies dedicated to aptamer design and modeling. We consider aptamers with different targets, such as proteins, antibiotics, organophosphates, nucleobases, amino acids, and drugs. During nucleic acid modeling and in silico design, a full set of in silico methods can be applied, such as docking, molecular dynamics (MD), and statistical analysis. The typical modeling workflow starts with structure prediction. Then, docking of target and aptamer is performed. Next, MD simulations are performed, which allows for an evaluation of the stability of aptamer/ligand complexes and determination of the binding energies with higher accuracy. Then, aptamer/ligand interactions are analyzed, and mutations of studied aptamers made. Subsequently, the whole procedure of molecular modeling can be reiterated. Thus, the interactions between aptamers and their ligands are complex and difficult to understand using only experimental approaches. Docking and MD are irreplaceable when aptamers are studied in silico.

AB - Aptamers are nucleic acid analogues of antibodies with high affinity to different targets, such as cells, viruses, proteins, inorganic materials, and coenzymes. Empirical approaches allow the design of in vitro aptamers that bind particularly to a target molecule with high affinity and selectivity. Theoretical methods allow significant expansion of the possibilities of aptamer design. In this study, we review theoretical and joint theoretical-experimental studies dedicated to aptamer design and modeling. We consider aptamers with different targets, such as proteins, antibiotics, organophosphates, nucleobases, amino acids, and drugs. During nucleic acid modeling and in silico design, a full set of in silico methods can be applied, such as docking, molecular dynamics (MD), and statistical analysis. The typical modeling workflow starts with structure prediction. Then, docking of target and aptamer is performed. Next, MD simulations are performed, which allows for an evaluation of the stability of aptamer/ligand complexes and determination of the binding energies with higher accuracy. Then, aptamer/ligand interactions are analyzed, and mutations of studied aptamers made. Subsequently, the whole procedure of molecular modeling can be reiterated. Thus, the interactions between aptamers and their ligands are complex and difficult to understand using only experimental approaches. Docking and MD are irreplaceable when aptamers are studied in silico.

KW - Aptamers

KW - Docking

KW - In silico design

KW - Molecular dynamics

KW - Molecular modeling

KW - PROTEIN DOCKING

KW - VITRO SELECTION

KW - MOLECULAR-DYNAMICS

KW - LIGAND-BINDING

KW - DNA-APTAMER

KW - HIGH-THROUGHPUT

KW - SIDE-CHAIN

KW - molecular dynamics

KW - docking

KW - molecular modeling

KW - in silico design

KW - FORCE-FIELD

KW - RNA APTAMER

KW - aptamers

KW - WEB SERVER

UR - http://www.scopus.com/inward/record.url?scp=85095998443&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/687f9aad-d4ad-3b70-9e76-734517cf9dc5/

U2 - 10.3390/ijms21228420

DO - 10.3390/ijms21228420

M3 - Review article

C2 - 33182550

VL - 21

SP - 1

EP - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 22

M1 - 8420

ER -