Contributors |
|
xv | |
Preface |
|
xvii | |
|
Part A Computational drug design |
|
|
|
1 Introduction of structural bioinformatics with respect to drug discovery |
|
|
|
|
|
|
|
3 | (8) |
|
|
3 | (2) |
|
1.2 Structural bioinformatics (SB) |
|
|
5 | (2) |
|
Frequently asked questions (FAQs) |
|
|
7 | (1) |
|
|
7 | (4) |
|
2 Target identification and validation |
|
|
|
|
|
|
11 | (2) |
|
2 Steps involved in in silico target identification |
|
|
13 | (8) |
|
Frequently asked questions (FAQs) |
|
|
19 | (1) |
|
|
19 | (2) |
|
|
|
|
|
|
|
21 | (10) |
|
|
21 | (1) |
|
1.2 Literature/chemical libraries |
|
|
21 | (1) |
|
1.3 Computational chemistry |
|
|
22 | (1) |
|
1.4 Steps involved in lead identification |
|
|
23 | (5) |
|
Frequently asked questions (FAQs) |
|
|
28 | (1) |
|
|
28 | (3) |
|
4 Lead identification and optimization |
|
|
|
|
|
|
31 | (1) |
|
|
31 | (1) |
|
|
31 | (1) |
|
|
32 | (4) |
|
3.1 Computer-aided drug design (CADD) |
|
|
32 | (1) |
|
|
33 | (1) |
|
3.3 Structure-based drug design (SBDD) |
|
|
33 | (1) |
|
3.4 Ligand-based drug design (LBDD) |
|
|
34 | (2) |
|
|
36 | (5) |
|
4.1 Steps involved in homology modeling using Modeller software |
|
|
36 | (4) |
|
4.2 Steps involved in homology modeling using I-TASSER online tool |
|
|
40 | (1) |
|
|
41 | (1) |
|
6 Steps involved in molecular docking |
|
|
41 | (1) |
|
7 AutoDock tool installation |
|
|
42 | (15) |
|
7.1 Steps involved in molecular docking using AutoDock tool |
|
|
42 | (15) |
|
8 Pharmacophore modeling using BRUSELAS |
|
|
57 | (8) |
|
8.1 Steps involved in pharmacophore modeling |
|
|
58 | (3) |
|
Frequently asked questions (FAQs) |
|
|
61 | (1) |
|
|
61 | (4) |
|
5 Molecular dynamics simulations |
|
|
|
|
|
|
65 | (1) |
|
|
66 | (1) |
|
3 Steps involved in molecular dynamics simulation of protein using Gromacs software |
|
|
67 | (9) |
|
4 Molecular dynamics simulation result analysis |
|
|
76 | (9) |
|
Frequently asked questions (FAQs) |
|
|
80 | (1) |
|
|
80 | (5) |
|
Part B Computational vaccine design |
|
|
|
6 An overview of vaccine design |
|
|
|
|
|
|
85 | (1) |
|
2 Key features of a potential vaccine |
|
|
85 | (1) |
|
3 Components of an ideal vaccine |
|
|
86 | (1) |
|
4 Role of bioinformatics in vaccine design |
|
|
87 | (1) |
|
5 An ideal vaccine design process |
|
|
87 | (6) |
|
5.1 Potential vaccine target identification |
|
|
88 | (1) |
|
5.2 B and T cell epitope prediction |
|
|
88 | (1) |
|
5.3 Linker and adjuvant selection |
|
|
88 | (1) |
|
5.4 Construct design and antigenicity/allergenicity prediction |
|
|
88 | (1) |
|
5.5 Structure prediction, protein-protein interactions and stability analysis |
|
|
89 | (1) |
|
5.6 Construct synthesis and cloning |
|
|
89 | (1) |
|
5.7 Expression, purification of the construct and biological assay |
|
|
89 | (1) |
|
Frequently asked questions (FAQs) |
|
|
89 | (1) |
|
|
90 | (1) |
|
|
90 | (3) |
|
7 Key steps in the selection of vaccine targets |
|
|
|
|
|
93 | (1) |
|
|
94 | (3) |
|
Frequently asked questions (FAQs) |
|
|
94 | (1) |
|
|
95 | (1) |
|
|
95 | (2) |
|
8 Epitope prediction and selection of linkers and adjuvant |
|
|
|
|
|
97 | (12) |
|
|
97 | (1) |
|
1.2 B-cell epitope prediction |
|
|
98 | (1) |
|
1.3 T-cell epitope prediction |
|
|
98 | (1) |
|
|
99 | (1) |
|
|
99 | (1) |
|
1.6 B-cell epitope prediction |
|
|
100 | (2) |
|
1.7 Steps involved in T-cell epitope prediction using IEDB |
|
|
102 | (3) |
|
Frequently asked questions (FAQs) |
|
|
105 | (1) |
|
|
106 | (1) |
|
|
106 | (3) |
|
9 Design of vaccine constructs |
|
|
|
|
|
|
109 | (12) |
|
|
109 | (1) |
|
1.2 Antigenicity, allergenicity, toxicity, solubility and stability prediction |
|
|
110 | (1) |
|
|
111 | (6) |
|
Frequently asked questions (FAQs) |
|
|
117 | (1) |
|
|
118 | (1) |
|
|
118 | (3) |
|
10 In silico validation through protein-protein docking |
|
|
|
|
|
121 | (14) |
|
1.1 Protein-protein., interaction |
|
|
121 | (1) |
|
1.2 Molecular dynamics of the protein-protein complex |
|
|
122 | (1) |
|
1.3 Steps involved in protein-protein interaction (PPI) using the HADDOCK server |
|
|
122 | (8) |
|
Frequently asked questions (FAQs) |
|
|
130 | (1) |
|
|
131 | (1) |
|
|
131 | (4) |
|
|
|
|
|
|
|
|
135 | (1) |
|
|
135 | (1) |
|
1.2 Component required for cloning |
|
|
135 | (1) |
|
|
136 | (1) |
|
2 PCR (polymerase chain reaction) |
|
|
136 | (3) |
|
3 Type of molecular cloning |
|
|
139 | (7) |
|
3.1 Restriction enzyme cloning |
|
|
139 | (1) |
|
|
140 | (4) |
|
|
144 | (2) |
|
|
146 | (19) |
|
4.1 Bacterial competent cell preparation and transformation |
|
|
146 | (1) |
|
|
147 | (1) |
|
4.3 Yeast cell preparation and transformation |
|
|
147 | (3) |
|
|
150 | (8) |
|
4.5 Insect cell transfection |
|
|
158 | (2) |
|
Frequently asked questions (FAQs) |
|
|
160 | (1) |
|
|
161 | (1) |
|
|
162 | (3) |
|
|
|
|
|
|
165 | (16) |
|
1.1 Key features of the Prokaryotic vs. Eukaryotic translation machinery |
|
|
165 | (1) |
|
1.2 E. coli-based protein expression |
|
|
165 | (10) |
|
1.3 Yeast expression system |
|
|
175 | (2) |
|
1.4 Mammalian cell line expression |
|
|
177 | (2) |
|
Frequently asked questions (FAQs) |
|
|
179 | (1) |
|
|
180 | (1) |
|
13 Protein purification and desalting |
|
|
|
|
|
|
|
181 | (2) |
|
|
181 | (2) |
|
2 Types of protein purification |
|
|
183 | (20) |
|
2.1 Affinity chromatography (AC) |
|
|
183 | (7) |
|
2.2 Ion exchange chromatography |
|
|
190 | (2) |
|
2.3 Gel filtration chromatography |
|
|
192 | (2) |
|
2.4 Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) |
|
|
194 | (3) |
|
|
197 | (2) |
|
Frequently asked questions (FAQs) |
|
|
199 | (1) |
|
|
200 | (3) |
|
|
|
|
|
|
|
203 | (8) |
|
|
203 | (6) |
|
Frequently asked questions (FAQs) |
|
|
209 | (1) |
|
|
210 | (1) |
|
|
|
|
|
|
1 Biophysical assay/methods |
|
|
211 | (14) |
|
|
211 | (3) |
|
1.2 Surface plasmon resonance (SPR) |
|
|
214 | (4) |
|
1.3 Circular dichroism (CD) |
|
|
218 | (2) |
|
Frequently asked questions (FAQs) |
|
|
220 | (1) |
|
|
220 | (5) |
|
|
|
16 Outline of animal study for lead/vaccine testing |
|
|
|
|
|
|
225 | (1) |
|
1 Selection of animal model |
|
|
226 | (1) |
|
|
226 | (1) |
|
|
226 | (1) |
|
|
226 | (1) |
|
|
226 | (1) |
|
|
226 | (1) |
|
|
227 | (1) |
|
|
227 | (1) |
|
|
228 | (1) |
|
4 Standard dose selection |
|
|
228 | (2) |
|
|
230 | (1) |
|
|
230 | (3) |
|
Frequently asked questions (FAQs) |
|
|
231 | (1) |
|
|
231 | (2) |
|
17 Evaluation of immunogenicity of vaccine candidates |
|
|
|
|
|
|
233 | (6) |
|
1.1 ELISA assays for quantification of antibody concentration |
|
|
233 | (1) |
|
1.2 Determination of T-cell immune response from mice |
|
|
234 | (1) |
|
1.3 Detection of cytokine profiling from mice |
|
|
235 | (1) |
|
1.4 Parasite inhibition assay for Plasmodium falciparum |
|
|
236 | (1) |
|
Frequently asked questions (FAQs) |
|
|
236 | (1) |
|
|
237 | (2) |
|
18 In-vitro evaluation of lead molecule |
|
|
|
|
|
|
239 | (8) |
|
1.1 Microscopy based parasite count |
|
|
239 | (3) |
|
1.2 PCR based parasite count |
|
|
242 | (1) |
|
1.3 Flow cytometry method for parasite count |
|
|
243 | (1) |
|
Frequently asked questions (FAQs) |
|
|
244 | (1) |
|
|
245 | (2) |
|
19 Medical physiological parameter for lead/vaccine testing |
|
|
|
|
|
|
247 | (16) |
|
|
248 | (3) |
|
|
251 | (2) |
|
1.3 Hematological indices |
|
|
253 | (1) |
|
1.4 Antioxidant parameters |
|
|
254 | (4) |
|
Frequently asked questions (FAQs) |
|
|
258 | (1) |
|
|
258 | (5) |
|
Part E Clinical trials and FDA approval |
|
|
|
20 Brief introduction of clinical research and trials |
|
|
|
|
|
|
|
263 | (4) |
|
Frequently asked questions (FAQs) |
|
|
265 | (1) |
|
|
265 | (2) |
|
21 An overview of IND, NDA, approval agencies and FDA post-marketing surveillance |
|
|
|
|
|
|
267 | (1) |
|
2 Investigational new drug (IND) |
|
|
268 | (1) |
|
3 New drug application (NDA) |
|
|
269 | (2) |
|
4 FDA post-marketing safety monitoring |
|
|
271 | (4) |
|
Frequently asked questions (FAQs) |
|
|
272 | (1) |
|
|
272 | (3) |
|
22 Introduction of intellectual property rights |
|
|
|
|
|
|
275 | (3) |
|
|
275 | (1) |
|
1.2 Trademarks and service mark |
|
|
276 | (1) |
|
|
276 | (1) |
|
1.4 Geographical indication (CI) |
|
|
277 | (1) |
|
1.5 Traditional knowledge |
|
|
277 | (1) |
|
|
278 | (1) |
|
2 How to fill the patent application in the US and India? |
|
|
278 | (5) |
|
2.1 Patent application filing in India |
|
|
278 | (1) |
|
2.2 Patent application filing in the US |
|
|
279 | (1) |
|
Frequently asked questions (FAQs) |
|
|
280 | (1) |
|
|
281 | (2) |
Index |
|
283 | |