Flap Tip Research Articles

Multiple Molecular Dynamics Simulations and Energy Analysis Unravel the Dynamic Properties and Binding Mechanism of Mutants HIV-1 Protease with DRV and CA-p2.

ABSTRACTPRS17, a variant of human immunodeficiency virus type I protease (HIV-1 PR), has 17 mutated residues showing high levels of multidrug resistance. To describe the effects of these mutated residues on the dynamic properties and the binding mechanism of PR with substrate and inhibitor, focused on six systems (two complexes of WT PR and PRS17 with inhibitor Darunavir (DRV), two complexes of WT PR and PRS17 with substrate analogue CA-p2, two unligand WT PR and PRS17), we performed multiple molecular dynamics (MD) simulations combined with MM-PBSA and solvated interaction energy (SIE) methods. For both the unligand PRs and ligand-PR complexes, the results from simulations revealed 17 mutated residues alter the flap-flap distance, the distance from flap regions to catalytic sites, and the curling degree of the flap tips. These mutated residues changed the flexibility of the flap region in PR, and thus affected its binding energy with DRV and CA-p2, resulting in differences in sensitivity. Hydrophobic cavity makes an important contribution to the binding of PR and ligands. And most noticeable of all, the binding of the guanidine group in CA-p2 and Arg8’ of PRS17 is useful for increasing their binding ability. These results have important guidance for the further design of drugs against multidrug resistant PR.IMPORTANCE Developing effective anti-HIV inhibitors is the current requirement to cope with the emergence of the resistance of mutants. Compared with the experiments, MD simulations along with energy calculations help reduce the time and cost of designing new inhibitors. Based on our simulation results, we propose two factors that may help design effective inhibitors against HIV-1 PR: (i) importance of hydrophobic cavity, and (ii) introduction of polar groups similar to the guanidine group.

Comparison of distally based sural artery and supramalleolar flap for coverage of dorsum of foot and ankle defects; a cross-sectional study of 53 patients

BackgroundSoft tissue defects over the foot and ankle region are most challenging in reconstructive surgery. Sural artery and supramalleolar flaps have been commonly used for the reconstruction of non-weight-bearing surfaces of the foot. This article aimed to evaluate the long-term outcome comparisons between a sural artery and Supramalleolar flap in the reconstruction of extensive defects of foot and ankle only. MethodsBetween 1996 and 2020, a retrospective analysis of 53 fasciocutaneous flaps (27 sural and 26 Supramalleolar) used for reconstruction of soft tissue defects of foot and ankle were reviewed in this study. The parameters included were demographics data, causes, site and size of the defect, flap size, hospital stay, complications, and outcomes in a pre-structured proforma. The clinical outcome was assessed by a Self-Designed Tool based on flap survival, coverage of defect, weight-bearing status, functional activities of daily living, and cosmetic appearance. Data were analyzed through SPSS version 25. ResultsAmong 53 flaps, the major cause of the defect was Trauma (60.4%). The maximum flap size harvested was 25*10 for sural and 20*8 cm for supramalleolar. Complications were seen in 8 (15%) cases in both flaps. Flap tip necrosis and venous congestion were seen in 4 cases. 2 each in Supramalleolar whereas 1 partial necrosis, 1 venous congestion, and 2 infections were seen in the sural artery flap. The flap survival rate in both flaps was 96.2%. Based on the self-designed Tool, flaps were graded Excellent in 43, Good in 8, and Fair in 2 cases. There was no case of Poor in both flaps. ConclusionCompared with the sural artery flap, the lateral supramalleolar flap demonstrated higher rates of functional outcomes although flap tip necrosis was higher in Supramalleolar.

Multiple Molecular Dynamics Simulations and Free-Energy Predictions Uncover the Susceptibility of Variants of HIV-1 Protease against Inhibitors Darunavir and KNI-1657.

HIV-1 protease (PR) is considered to be the main targets of anti-AIDS drug design because of its role in the proteolytic processing of viral polyproteins. However, the emergence of drug-resistant HIV has become a major problem in the therapy of HIV-1-infected patients. Focused on the complexes of wild type (WT) PR and two mutant PRs (V32I/L33F/I54M/V82I and V32I/L33F/I54M/I84 V) with inhibitors Darunavir (DRV) and KNI-1657 (KNI), respectively, we have conducted research on the conformational dynamics and the resistance mechanism caused by residue mutations through multiple molecular dynamics (MD) simulations combined with an energy (MM-PBSA and solvated interaction energy (SIE)) prediction. The results indicate that mutated residues of PR alter the distance between flap regions and catalytic sites, the volume of the inner catalytic site, and the curling degree of the flap tips, thereby affecting DRV and KNI inhibitor binding to PR. These mutated residues reduced the binding affinity of the two mutant PRs to DRV, resulting in drug resistance, whereas the two mutant PRs increase the binding affinity with KNI, indicating they enhance the sensitivity to KNI. Compared with the WT PR, the changes in van der Waals interaction and electrostatic interaction in the two variant PRs play a vital part in the binding of PR with DRV and KNI. These results may supply valuable guidance for the design of anti-AIDS drugs targeting PR.

Strategy of harvesting extended thoracodorsal artery perforator flaps for resurfacing the large soft-tissue defects of extremities

The authors presented their strategy to harvest extended thoracodorsal artery (TDA) perforator flaps for resurfacing the large soft-tissue defects of extremities. Thirty-three free extended TDA perforator flaps were harvested in 33 patients. The mean flap size was 145.2 cm2. The maximal flap length and the width were 30 cm and 10 cm, respectively. The color Doppler sonography (CDS) was used for preoperative assessment of perforators. Indocyanine green angiography (ICGA) was used for intraoperative assessment of flap viability in three patients. The vascular thrombosis, donor-site scar widening, and delayed recipient-site wound healing were not significantly related to the patient and flap characteristics. Flap tip or partial necrosis was significantly related to age and peripheral vascular disease. True positive rate, false negative rate, and positive predictive value of CDS for perforator identification were not different significantly between attending surgeon and residents. In the distance discrepancy of CDS, significant difference was found based on the classifications of perforator size, perforator type, and sonographic operator. The ICGA identified a hypoperfused distal area in a 30 cm long flap. The CDS locates the TDA perforators more precisely when scanned by experienced hands, in larger size or septocutaneous perforators. Using reliable and more perforators, applying muscle-sparing technique, considering suprafascial course of perforator and proper flap orientation are helpful in harvesting extended TDA perforator flaps. ICGA is an option for assessing flap viability, especially in elders and patients with peripheral vascular diseases.

Investigating potency of TMC-126 against wild-type and mutant variants of HIV-1 protease: a molecular dynamics and free energy study

ABSTRACT A detailed computational study was performed to investigate the conformational changes of flap region and the mechanism underlying the binding of the inhibitor TMC-126 to HIV-1 protease (PR1) and its mutant variants through molecular dynamics simulations in conjunction with the molecular mechanics Poisson–Boltzmann (MM-PBSA) free energy calculation. Further, we have studied the effectiveness of the inhibitor against HIV-2 protease (PR2). The MM-PBSA calculation suggests that TMC-126 loses its potency against mutant variants and PR2 compared to wild-type PR1 mainly due to the loss in intermolecular electrostatic interactions. The potency of the inhibitor decreases in the order: wild type PR1 > M46L > MDR20 > I50V > PR2 > V32I > A28S. Our study reveals that the flap of PR1 adopts a semi-open conformation due to the mutation I50V or MDR20. The dissimilar nature of the movement of the flap tip of both monomers is evident from the dynamic cross-correlation map. The protein structural network analysis displays that mutation causes structural rearrangements and changes the communication path between residues. Overall, we believe our study may help explore and accelerate the development of novel HIV-1/HIV-2 protease inhibitors with better potency.

Use of the O-Z Flap to Repair Scalp Defects After Cancer Tumor Resection.

Large benign and malignant tumors in the scalp cannot be sutured directly after resection. Instead, skin grafting or skin flap repair is the most commonly used techniques. Local tissue depression and lack of hair growth are some of the drawbacks associated with these techniques. The use of a modified local flap (the O-Z flap) may effectively overcome these issues. To explore the application of O-Z flap in wound repair after excision of benign and malignant tumors of the scalp. Between April 2016 and November 2017, the authors treated 6 patients with scalp tumors. They underwent round or oval radical tumor resection with negative margins. Tumor specimens were diagnosed by cryosection during operation. According to the wound defect size and location, surrounding scalp looseness, and hair distribution, 2 rotating flaps in opposite directions were formed on the left and right sides or front and back of the wound. Subsequently, the skin flaps were rotated in opposite directions to repair the wound. The scalp tumors comprised 2 cases of basal cell carcinoma, 2 cases of squamous cell carcinoma, 1 case of hair sheath carcinoma, and 1 case of epidermoid cyst. After complete tumor resection, the wound defect area was between 3.0 cm × 3.5 cm and 5.0 cm × 6.0 cm. After operation, approximately 6% of the tip of the skin flap was necrotized. The wounds healed after 4 weeks of dressing treatment. All skin flaps survived in stage I and no complications occurred. All patients were followed up for 3 to 12 months; the scalps were in good condition and no tumor recurrence was found. The use of the O-Z flap to repair scalp wounds offers flexible design, good blood circulation, uniform tension, and good hair growth after operation; thus, this technique is suitable for wound repair following scalp tumor resection.

Total Superficial Parotidectomy: Pros and Cons

Background: Total superficial parotidectomy is the most commonly used approach in excising the tumors that affect the superficial lobe of the parotid gland, whether they're benign or malignant. The aim of the study is to evaluate the benefits and drawbacks of total superficial parotidectomy for parotid gland tumors within five years of follow-up. Patients and methods: Nineteen patients with lateral facial swelling affecting the parotid region were included in this study. All of them operated under general anesthesia with oral endotracheal intubation, where Modified Blair Incision (lazy S incision) was utilized in all cases. Anterograde dissection with facial nerve identification was accomplished with total superficial parotidectomy. Results: Fifteen patients had benign parotid tumors, and only four patients had well-differentiated mucoepidermoid carcinoma. Skin necrosis of the distal tip of the postauricular flap was the most commonly observed postoperative complication, it occurred in five patients; facial nerve weakness was observed in the another three patients. Conclusions: total superficial parotidectomy is an efficient, safe technique for benign and malignant tumors affecting the superficial lobe of the parotid gland with minimum postoperative complications.

To study and analyse various management options of middle one third leg defects

Aim: To study and analyse various management options of middle one third leg defects. Methodology: This Prospective Clinical study conducted in the department of Plastic and Reconstructive surgery, Osmania General Hospital, Hyderabad, Telangana includes 30 cases of middle one third of leg defects admitted between November 2016 to November 2018. Results: Age of the patients ranged between 20 and 60 years with a mean age of 34years. 27 patients were males and 3 were females. 18(60%) patients had middle one third defects of right leg and 12(40%) patients had middle one third defects of left leg. Leg defect was on anteromedial site in 21(70%) patients and anterolateral site in 9 (30%) patients. Trauma (Road traffic accidents) was the cause in 26 (86.6%) patients and post operative defect exposing Implant in 3(10%) patients. The size of the defect ranged from 4 sq.cm to36sq.cm. Time of presentation to hospital ranged from less than 1week to 1year after injury. Tibia was the common component exposed in all patients. Associated Grade III B compound fractures with external fixator were present in 18(60%) patients. Minor complications were seen in 4(13.3%) patients. Partial Graft loss was present in 1 patient (3.3%) over flap donor site which was managed conservatively. Flap tip necrosis (1cm) was present in 3 patients which was debrided and grafted. The follow up period was up to six months with adequate physiotherapy. In most of the cases, satisfactory results with good aesthetic appearance was present. Conclusion: There are many related advantages of this flaps such as being a simple technique allowing full tissue coverage in a one‑stage operation, and it is present in the dissection field. Full tissue coverage, functional recovery, and good esthetic results are achieved with minimum damage to the donor site. In addition, the surgical procedure is relatively short and easy to perform, and it does not require microsurgical skills and instruments.

Structural basis for activation of Swi2/Snf2 ATPase RapA by RNA polymerase.

RapA is a bacterial RNA polymerase (RNAP)-associated Swi2/Snf2 ATPase that stimulates RNAP recycling. The ATPase activity of RapA is autoinhibited by its N-terminal domain (NTD) but activated with RNAP bound. Here, we report a 3.4-Å cryo-EM structure of Escherichia coli RapA–RNAP elongation complex, in which the ATPase active site of RapA is structurally remodeled. In this process, the NTD of RapA is wedged open by RNAP β' zinc-binding domain (ZBD). In addition, RNAP β flap tip helix (FTH) forms extensive hydrophobic interactions with RapA ATPase core domains. Functional assay demonstrates that removing the ZBD or FTH of RNAP significantly impairs its ability to activate the ATPase activity of RapA. Our results provide the structural basis of RapA ATPase activation by RNAP, through the active site remodeling driven by the ZBD-buttressed large-scale opening of NTD and the direct interactions between FTH and ATPase core domains.

Revertant mutation V48G alters conformational dynamics of highly drug resistant HIV protease PRS17

Drug resistance is a serious problem for controlling the HIV/AIDS pandemic. Current antiviral drugs show several orders of magnitude worse inhibition of highly resistant clinical variant PRS17 of HIV-1 protease compared with wild-type protease. We have analyzed the effects of a common resistance mutation G48V in the flexible flaps of the protease by assessing the revertant PRS17V48G for changes in enzyme kinetics, inhibition, structure, and dynamics. Both PRS17 and the revertant showed about 10-fold poorer catalytic efficiency than wild-type enzyme (0.55 and 0.39 μM−1min−1 compared to 6.3 μM−1min−1). Clinical inhibitors, amprenavir and darunavir, showed 2-fold and 8-fold better inhibition, respectively, of the revertant than of PRS17, although the inhibition constants for PRS17V48G were still 25 to 1,200-fold worse than for wild-type protease. Crystal structures of inhibitor-free revertant and amprenavir complexes with revertant and PRS17 were solved at 1.3–1.5 Å resolution. The amprenavir complexes of PRS17V48G and PRS17 showed no significant differences in the interactions with inhibitor, although changes were observed in the conformation of Phe53 and the interactions of the flaps. The inhibitor-free structure of the revertant showed flaps in an open conformation, however, the flap tips do not have the unusual curled conformation seen in inhibitor-free PRS17. Molecular dynamics simulations were run for 1 μs on the two inhibitor-free mutants and wild-type protease. PRS17 exhibited higher conformational fluctuations than the revertant, while the wild-type protease adopted the closed conformation and showed the least variation. The second half of the simulations captured the transition of the flaps of PRS17 from a closed to a semi-open state, whereas the flaps of PRS17V48G tucked into the active site and the wild-type protease retained the closed conformation. These results suggest that mutation G48V contributes to drug resistance by altering the conformational dynamics of the flaps.

Clinical Observations of a Surgical Method Comprising a Combination of Cross Flap and Autologous Auricular Cartilage Transplantation in the Treatment of Type I to III Congenital Concha-Type Microtia.

The present study attempted to investigate the clinical efficacy of a surgical method involving a combination of cross flap with autologous auricular cartilage transplantation in the treatment of type I to III congenital concha-type microtia. The present retrospective study was conducted on the clinical and postoperative data of 50 patients with unilateral type I to III concha-type microtia treated with a combination of cross flap and autologous auricular cartilage transplantation at the Plastic Surgery Hospital of Chinese Academy of Medical Sciences from January 2018 to December 2021. The postoperative perimeters of malformed ears were significantly larger than the preoperative perimeters (P < .05). Of the total, 2 patients exhibited incision dehiscence, 3 patients exhibited incision infection, 2 patients exhibited flap hematoma, and 1 patient exhibited ischemic necrosis at the flap tip. The satisfaction rate of the patients and their families was 100%. The surgical method involving a combination of cross flap and autogenous auricular cartilage transplantation was effective in treating patients with type I to III congenital concha-type microtia, and therefore, this surgical approach can be applied widely to correct this deformity.

Empirical estimation of engine-integration noise for high bypass ra-tio turbofan engines

To investigate the impact of installation on jet noise from modern high-bypass-ratio turbofan engines, a model-scale noise experiment with a jet propulsion system and a fuselage model in scale was conducted in the anechoic wind tunnel of ONERA, CEPRA 19. Two area ratios (an area of the secondary nozzle over an area of the primary nozzle), 5 and 7, and various airframe configurations such as wing positions relative to the tip of the engine nacelle and flap angles, were considered. Based on the analysis of experimental data, an empirical model for the prediction of engine installation noise was proposed. The model comprises two components: one is the interaction be-tween the jet and the pressure side of the wing, and the other is the interaction between the jet and the flap tip. The interaction between the jet and the pressure side of the wing contributes to the noise at the low frequencies (≤ 1.5 kHz), and the interaction between the jet and the flap tip con-tributes to the noise at the high frequencies. The proposed model showed a good agreement with the experimental data.

The three-point buried corner stitch: A method to prevent depression of the flap tip and railroad marks

The three-point buried corner stitch: A method to prevent depression of the flap tip and railroad marks

Genicular axial pattern flap for coverage of a hind limb defect caused by dog bites in a ewe

AbstractA ewe was referred with severe dog bite wounds after unsuccessful attendance in a first opinion surgery. A large, complex, contaminated wound was evident in the medial surface of the left tibia. Initial management included lavage, surgical debridement, suturing of ruptured muscles and bandaging. Staged debridement was performed repeatedly 7, 14 and 21 days after initial presentation, while open wound management was carried out for 6 weeks. When the left hind limb wound was covered with healthy granulation tissue, the defect was closed with a genicular axial pattern skin flap. Post‐operatively, antibiotics and analgesics were administered; bandages were applied. Flap tip oedema and partial thickness skin loss concerning the epidermis were observed. The ewe recovered after 40 days of post‐operative hospitalisation. On re‐examination, 1 year after initial admission, no complications or lameness was reported. Although therapeutic management required extensive surgical attention and long post‐operative care, the final outcome was favourable.

Cantilever-centric mechanism of cooperative non-active site mutations in HIV protease: Implications for flap dynamics

The HIV-1 protease is an important drug target in antiretroviral therapy due to the crucial role it plays in viral maturation. A greater understanding of the dynamics of the protease as a result of drug-induced mutations has been successfully elucidated using computational models in the past. We performed induced-fit docking studies and molecular dynamics simulations on the wild-type South African HIV-1 subtype C protease and two non-active site mutation-containing protease variants; HP3 PR and HP4 PR. The HP3 PR contained the I13V, I62V, and V77I mutations while HP4 PR contained the same mutations with the addition of the L33F mutation. The simulations were initiated in a cubic cell universe containing explicit solvent, with the protease variants beginning in the fully closed conformation. The trajectory for each simulation totalled 50 ns. The results indicate that the mutations increase the dynamics of the flap, hinge, fulcrum and cantilever regions when compared to the wild-type protease while in complex with protease inhibitors. Specifically, these mutations result in the protease favouring the semi-open conformation when in complex with inhibitors. Moreover, the HP4 PR adopted curled flap tip conformers which coordinated several water molecules into the active site in a manner that may reduce inhibitor binding affinity. The mutations affected the thermodynamic landscape of inhibitor binding as there were fewer observable chemical contacts between the mutated variants and saquinavir, atazanavir and darunavir. These data help to elucidate the biophysical basis for the selection of cooperative non-active site mutations by the HI virus.

Designing and utilizing 3D-printed skin incision guides during the first Dutch bilateral hand-arm transplantation

To preoperatively plan skin incision in the case of the first Dutch bilateral hand-arm transplantation. A bilateral hand-arm transplantation has been performed for the first time in the Netherlands in 2019. In the context of preparation for this surgical procedure, the optimal patient-specific skin flap was determined. Skin flaps should be properly matched between donor and recipient to ensure sufficient tissue for the approximation of skin over the tendon anastomosis, adequate distal tip perfusion, and esthetics. Preoperatively, stereophotogrammetry was obtained from the upper extremities of the patient and a volunteer with similar body physique. Skin flap dimensions were determined for each extremity, which resulted in patient-specific incision patterns. Combining this digital information yielded practical skin incision guides for both the donor and acceptor arms. Finally, the computer-aided designs were 3D printed. The 3D prints were convenient to utilize in both shaping the donor flaps as in preparing the acceptor extremities, taking only a few seconds during precious ischemia time. There was sufficient skin flap perfusion, and the wound-healing followed an uncomplicated course. No corrections were made to the initial skin incisions. Three-dimensional printed templates were successfully utilized in the first Dutch bilateral hand-arm transplantation. We believe its usage increased time efficiency, improved the match of skin flaps in donor and recipient arms, and allowed us to control the amount of skin surplus without skin flap tip necrosis. In these procedures where time is of the essence, we believe preoperative planning is imperative for its success.

Long V-Y advancement technique for large nipple reconstruction in Asian women.

Previously reported nipple-areolar complex reconstruction (NAR) methods involve multiple incisions and wide skin redraping, which increase retraction forces and heighten the risk of nipple-areolar complex (NAC) flattening. We introduce a NAR method using the long V-Y advancement technique that can overcome these disadvantages. A V-shaped flap is designed with the width of the flap base 4–5 mm larger than the diameter of the normal nipple. The flap length is designed to be at least 2.5 times its width. Dissection is performed to the top of the artificial dermal matrix or muscle layer. The nipple is constructed with the same projection as the contralateral side by folding the elevated flap. The tip of the elevated flap is apposed in the middle of the donor defect to minimize the deformity during donor site closure. A 3-point skin suture is applied to the upper third of the folded flap to mold its shape. Using this long V-Y advancement technique, we successfully decreased skin tension in NAC flaps and improved the maintenance of reconstructed nipple projection. The long V-Y advancement technique provides an easy, simple NAR method, effectively maintaining longer nipple projections and reducing breast deformities, especially in Asian women with relatively large nipples.

Supraclavicular Artery Flap versus Skin Graft: Which Is a Better Reconstructive Tool for Managing Post-Burn Contractures in the Neck.

BACKGROUNDBurn in developing countries still has high burden of inadequately managed severe burns. This study compared supraclavicular artery flap and skin graft in managing neck post-burn contractures.METHODSIn National Institute of Rehabilitation Medicine and Pakistan Institute of Medical Sciences, Islamabad, Pakistan, 30 patients with neck post-burn contractures were enrolled. Half of patients randomly underwent supraclavicular artery flap and half received skin graft. The outcome measures including initial improvement in neck extension, patient’s satisfaction with color-texture-match and recurrent contracture formation rate were assessed.RESULTSAmong patients, 80% were female and 20% were male. Preoperatively, each group had post-burn contractures of grade II among 26.66% of patients, grade III among 60% and grade III among 13.3%. Postoperatively after three months in the two groups, 86.66% improved to grade I and 13.3% improved to grade II. Patient’s satisfaction with color-texture was 84.66% in supraclavicular artery flap group, whereas it was 42.66% for skin graft group. Complications were hypertrophic scar at donor site (13%) and flap tip necrosis (6.66%) in supraclavicular artery flap group. In skin graft group, partial skin graft loss was noticed among 33% of patients and delayed healing of donor site among 20%. The recurrent contracture formation rate at one year was 73.33% in skin graft group, whereas there was no case of recurrent contracture in supraclavicular artery flap group. CONCLUSIONSupraclavicular artery flap was superior to skin graft in managing post-burn neck contractures. It provided better color-texture match and was associated with no recurrence of contracture formation.

Transposition Flaps for Reconstruction of Perianal Skin Defects After Tumor Resection

ABSTRACT Objective To investigate the application of transposition flaps in the reconstruction of perianal skin defects after tumor resection. Methods From September 2018 to December 2019, 16 cases of perianal skin defects were repaired with unilateral or bilateral transposition flaps. The wound size before closure ranged from 4 cm × 8 cm to 7 cm × 10 cm. Fourteen patients achieved primary healing. Wound dehiscence occurred in one patient at the flap tip, whereas a slight infection occurred in another patient, which healed after a dressing change. During the follow-up period of 3–6 months, all patients were satisfied with the perianal area both aesthetically and functionally. Conclusion Transposition flaps are a promising option for the repair of perianal skin defects after tumor removal. Owing to the simplicity of the flap design, the wide popularity of this flap type among surgeons is anticipated.

Understanding the Binding Mechanism of Antagonist (AZD3293) Against BACE-1: Molecular Insights into Alzheimer’s Drug Discovery

Background:β-site amyloid precursor protein cleaving enzyme (BACE 1) is the ratelimiting enzyme in the formation of neurotoxic β-amyloid (Aβ) residues (Aβ1-40 or Aβ1-42) considered as key players in the onset of Alzheimer’s Disease (AD). Consequently, BACE 1 is one of the principal targets of anti-AD therapy with many small molecule BACE 1 inhibitors (BACE 1Is) in clinical trials. AZD3293 (Lanabecestat) is a BACE 1I that concluded in phase 2/3 clinical trials. Due to the limited knowledge about the interaction of this drug with the BACE 1 enzyme, in the present study, we performed comprehensive Molecular Dynamics (MD) analysis to understand the binding mechanism of AZD3293 to BACE 1.Methods:A production run of 120 ns is carried out and results are analysed using Root Mean Square Deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) to explain the stability of enzyme ligand complex. Further, the distance (d1) between the flap tip (Thr72) and the hinge residue of the flexible loop (Thr328), in relation to θ1 (Thr72–Asp228- Thr328), and to the dihedral angle δ (Thr72-Asp35-Asp228-Thr328) were measured.Results:The presence of the ligand within the active site restricted conformational changes as shown by decreased values of RMSF and average RMSD of atomic positions when compared to the values of the apoenzyme. Further analysis via the flap dynamics approach revealed that the AZD3293 decreases the flexibility of binding residues and made them rigid by altering the conformational changes.Conclusion:The prospective binding modes of AZD3293 from this study may extend the knowledge of the BACE 1-drug interaction and pave the way to design analogues with similar inhibitory properties needed to slow the progression of Alzheimer’s disease.